The intestinal microbiota, comprised of bacteria, archaea, and phages, inhabits the gastrointestinal tract of the organism. Male reproductive sterility is currently a prominent topic in medical research. Increasing research suggests that gut microbiota dysbiosis can result in various reproductive health problems. This article specifically investigates the impact of gut microbiota dysbiosis on male reproductive infertility development. Gut microbiota imbalances can disrupt the immune system and immune cell metabolism, affecting testicular growth and sperm production. This dysfunction can compromise the levels of hormones produced and secreted by the endocrine glands, affecting male reproductive health. Furthermore, imbalance of the gut microbiota can disrupt the gut-brain-reproductive axis, resulting in male reproductive infertility. This article will explore how the imbalance of the gut microbiota impacts male reproductive infertility through immune regulation, endocrine regulation, and interactions of the gut-brain-reproductive axis, concluding with recommendations for prevention and treatment.

Background: Over the past years, there has been a rise in the incidence of type 1 diabetes, partic-ularly among younger individuals. This concerning trend has prompted investigations into po-tential contributing factors, with intestinal dysbiosis emerging as a likely culprit for the escalating annual rates of the disease; (2) Methods: We conducted a retrospective ecologic correlational study involving 37 children from the southern region of Romania between 2019-2021. All participants were within the first six months following the onset of the disease; (3) Results: In the microbiota of the patients we observed a dysbiosis marked by an overabundance of bacteria (Clostridium coccoides, Faecalibacterium, Bacterioides, Enterobacteriaceae) and fungi, compared to the healthy control group. The Spearman correlation revealed a positive association between the presence of Bacteroides (p=0.0442), Butyricicoccus (p=0.0164), and Clostridium leptum (p=0.0023) with recent diabetes onset. Furthermore, a significant correlation was observed between younger age at onset and the pres-ence of Butyricicoccus (p=0.019). The use of antibiotics in the month preceding admission was linked to the presence of fungi in the microbiota (Candida, p=0.0442); (4) Conclusions: The dysbiosis of Romanian type 1 diabetes children correlates with inflammation, more severe onset of the disease and other au-toimmune diseases.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) has the potential to alleviate alcoholic liver injury may play essential roles in treating for alcohol-exposed liver disease, however, the hepatoprotective effects and mechanisms remain unclear. In this study, the hepatoprotective effects of HDPs and its potential mechanisms were investigated in alcohol-exposed mice by liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. By applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria while significant increases in Firmicutes at the phylum level, and increased Lactobacillus abundance while decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid metabolism and glycerophospholipid metabolism and identified two important metabolites C00157 and C04230 involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs has a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

Prostate cancer is the second leading cause of death in males in America, with advanced prostate cancers exhibiting a 5-year survival rate of only 32%. Castration-resistance is often developed during the course of treatment, though its influences require further understanding. This study explores the human microbiome for its implications in castration-resistance and metastasis in prostate cancer. RNA sequencing data was downloaded for bone and soft tissue biopsies of patients with metastatic castration-resistant prostate cancer. These sequences were mapped to bacterial sequences to yield species-level abundance approximations. Numerous species were found to correlate to the expression of known markers of castration-resistance, including AR, PI3K, and AKT. Castration-resistance-associated signaling pathways were also enriched with these species, including PI3K-AKT signaling and endocrine resistance. For their implications in cancer aggression and metastasis, cancer stem cell markers were further explored for relation to these species. EGFR and SLC3A2 were widely downregulated with greater abundance of most species. Our results suggest that the microbiome is heavily associated with castration-resistance and stemness in prostate cancer. By considering the microbiome’s importance in these factors, we may better understand the highly aggressive and highly invasive nature of prostate cancer, allowing for needed improvement in the treatment of this disease.

: Cattle farming is an ancient practice, with roots in the early Neolithic era that has retained its status in the food industry today, with global beef market revenue amounting to $385.7B, as of 2018. Hence, cattle maintenance is naturally essential to cater to nutritional requirements of modern civilization. This extensive review aims to provide a holistic overview of cattle microbiome, analysing the native microbial composition within respiratory tract, gastrointestinal tract, reproductive tract, and skin. The dysbiosis associated with various diseases such as bovine respiratory disease, bovine digital dermatitis, mastitis, Johne's disease, uterine diseases (metritis and endometritis) and metabolic disorders (ruminal acidosis and ketosis) has been discussed. Moreover, various non-antibiotic microbial therapies including phage therapy, prebiotics and probiotics have been examined as potential means to reduce disease-associated dysbiosis. In general, this review highlights the importance of the microbiome in maintenance of health in cattle and its potential in alleviating bovine diseases, with an aim to enhance cattle health and production.

Salmonella infections can lead to intestinal inflammation and metabolic disorders in birds. However, whether ARA metabolism is involved in Salmonella-induced intestinal inflammation remains unclear. This experiment investigated the changes in cecal flora and arachidonic acid (ARA) metabolism in Hainan Wenchang chickens infected with S. Typhimurium using 16s rDNA sequencing and targeted metabolomics. The results showed that the levels of ARA metabolites were increased in the cecum tissue of Wenchang chickens after infection with S. Typhimurium, including prostaglandin E2, prostaglandin F2α, lipoxin A4, ±8(9)-EET, ±11(12)-EET, and ±8,9-DiHETrE. The content of key enzymes for ARA production and metabolism (PLA2 and COX-2) in chicken cecum tissues was increased after S. Typhimurium infection. The relative mRNA levels of inflammatory factors were also increased after infection, including IFN-γ, TGF-β1, IL-4, and IL-6. In HD11 cells, the use of a cyclooxygenase (COX) inhibitor reduced the increased levels of COX-2 and PGF2α induced by S. Typhimurium infection and effectively reduced the inflammatory response. In addition, the number of beneficial genera (e.g., Bifidobacterium, Lactobacillus, and Odorobacterium) in the cecum of Wenchang chickens was significantly reduced after infection with S. Typhimurium. In this study, we revealed the structure of the cecal flora of Wenchang chickens infected with S. Typhimurium and demonstrated that S. Typhimurium can mediate the onset and development of intestinal inflammation through the activation of the metabolic pathway of ARA cyclooxygenase in Wenchang chickens. The results can provide data support and theoretical support for the prevention and control of avian salmonellosis.

Recent interest in intestinal hormones has risen with the idea that they modulate glucose tolerance and food intake through a variety of mechanisms, and such hormones like peptide YY (PYY), ghrelin, glucagon-like peptide (GLP)-1 and 2, and cholecystokinin (CKK) are therefore excellent therapeutic candidates for the treatment of diabetes and obesity. Furthermore, in the recent years, multiple studies suggest that the microbiota is critically important for normal host functions, while impaired host microbiota interactions contribute to the pathogenesis of numerous common metabolic disorders. In this study, we considered the nutraceutical effects of β-glucans added to pasta at the concentration of 6g\100g. Ten participants have been recruited and hematochemical analyses and intestinal hormones tests have been performed before and after 30 days of pasta intake. Stool specimens have been studied for Lactobacillus Fermentum, Lactobacillus acidophilus, Lactobacillus salivarius, Bifidobacterium longum, and Enterococcus faecium presence before and after 30 days of nutritional intervention. After 30 days of regular intake of pasta enriched by β-glucans results have been evaluated. In conclusion, pasta prepared from barley flour enriched with β-glucans at 6% exhibit promising responses on glucose metabolism, on intestinal hormones responses and on microbiota modification.

In the world, migraine is one of the most common cause of disability in adults. To date, there is no a single cause for this disorder, but rather a set of physio-pathogenic triggers, in combination with a genetic predisposition. Among factors related to the migraine onset, a crucial role seems to be played by gut dysbiosis. In fact, it has been demonstrated how the intestine is able to modulate the central nervous system activities, through the gut-brain axis, and how gut dysbiosis can influence neurological pathologies, including migraine attacks. In this contest, in addition to migraine conventional pharmacological treatments, attention has been paid to an adjuvant therapeutic strategy based on different nutritional approaches and lifestyle changes able to positively modulate the gut microbiota composition. In fact, the restoration of the balance between the different gut bacterial species, the reconstruction of the gut barrier integrity and the control of the release of gut-derived inflammatory neuropeptides, obtained through specific nutritional patterns and lifestyle changes, represent a possible beneficial additive therapy for many migraine subtypes. Herein, this review explores the bi-directional correlation between migraine and the main chronic non-communicable diseases, like diabetes mellitus, arterial hypertension, obesity, cancer and chronic kidney diseases, whose link is represented by gut dysbiosis.

Esophageal cancer is an extremely deadly tumor that accounts for 5% of all cancer deaths. The two main subtypes of the disease are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). To date, few studies analyse EAC for transcriptional signatures associated with diagnosis and/or prognosis, while most focus on the analysis of transcriptional profiles of ESCC. In this study, we used single-cell RNA sequencing (scRNA-seq) analysis of CD45+ cells enriched from Tumors and matched Non Tumor tissues from therapy naїve patients to identify all types of immune cells present in tumor immune infiltrate and its transcriptional profile. In addi-tion, we analysed the entire transcriptome in a cohort of 23 patients whose tissue biopsies were taken from Tumors and matched with Non Tumor tissue. The transcriptional signatures we obtained were then used to stratify a large cohort of TCGA EAC patients, demonstrating a strong association with their prognosis, as well as the ability to predict a patient's clinical outcome and better define the prognosis of EAC after surgery. In addition, these features may lead patients to effective therapies including immunotherapy approaches.

Abstract: Background: The gut microbiota, a diverse community of microorganisms in the gastrointestinal tract, is essential for human health, primarily through nutrient metabolism and production of anti-inflammatory short-chain fatty acids. Dysbiosis, a disruption in microbial composition, is linked to diseases like inflammatory bowel disease, colorectal cancer, obesity, diabetes, asthma, and allergies. Dietary habits significantly influence gut microbiota diversity, with balanced diets crucial for maintaining microbial equilibrium. Culinary herbs and spices, known for their antioxidant and antimicrobial properties, may positively modulate the gut microbiota by inhibiting inflammation, stimulating beneficial bacteria, and exhibiting prebiotic effects. Methods: A comprehensive literature search was conducted using the PubMed database to identify relevant research articles on the impact of culinary spices on the gut microbiome. The search terms included "culinary spices," "gut microbiome," "gut modulation," "gut dysbiosis," "common spices," and "gut health." Thirty-five articles published between 2016 and 2024 were reviewed, with eight directly addressing the effects of culinary spices on gut microbiome modulation. Priority was given to peer-reviewed journals and reputable scientific sources. Results: Studies demonstrate that mixed spices and individual spices like ginger, turmeric, and chili can induce favorable changes in gut microflora, promoting beneficial probiotics and inhibiting pathogenic bacteria. Spices such as turmeric and curcumin exhibit potent anti-inflammatory properties, contributing to their protective effects against chronic diseases like colon cancer and metabolic disorders. Conclusions: Incorporating culinary spices into dietary interventions is important for overall well-being. Further research is needed to elucidate the mechanisms of action and optimize the therapeutic applications of spices in clinical settings.

Leptospirosis is an important zoonotic disease, causing about 60,000 deaths annually. One of the reasons for the severe course of leptospirosis is a cytokine storm, which develops as a result of an excessive immune response. The gut microbiota that resides in the gastrointestinal tract provides essential health benefits to its host, particularly by regulating immune homeostasis and a bidirectional relationship with many internal organs. A change in the gut microbiota can be caused not only by antibiotics, but also by infectious agents such as the coronavirus or the flu virus. It is known that L. interrogans can change the microbiota of mice. Thus, gut dysbiosis in leptospirosis can affect the clinical course of the disease, through the gut–organ axis. Modulation of intestinal microbiota by probiotics and/or fecal microbiota transplantation in leptospirosis may become an important area of scientific research.

Atherosclerosis is a leading cause of cardiovascular disease and mortality worldwide. Alterations in the gut microbiota composition, known as gut dysbiosis, have been shown to contribute to atherosclerotic cardiovascular disease (ACVD) development through several pathways. Disruptions in gut homeostasis are associated with activation of immune processes and systemic inflammation. The gut microbiota produces several metabolic products, namely trimethylamine (TMA), which is used to produce the proatherogenic metabolite trimethylamine-N-oxide (TMAO). Short chain fatty acids (SCFAs), including acetate, butyrate, and propionate, and certain bile acids (BAs) produced by the gut microbiota lead to inflammation resolution and decrease atherogenesis. Chronic low-grade inflammation is associated to common risk factors for atherosclerosis, including metabolic syndrome, type 2 diabetes mellitus (T2DM), and obesity. Novel strategies for reducing ACVD include the use of nutraceuticals such as resveratrol, modification of glucagon-like peptide 1 (GLP-1) levels, supplementation with probiotics, and administration of prebiotic SCFAs and BAs. Investigation into the relationship between the gut microbiota and its metabolites, and the host immune system could reveal promising insight into ACVD development, prognostic factors, and treatments.

Producing translucent eggs has been found to reduce the quality and safety of the eggs produced., as well as the demand from consumers. However, the intestinal function and the molecular mechanism for the production of translucent eggs remain uncertain. A total of 120 eggs were allocated into two groups, one for the translucent egg group (group T) and one for the normal group (group C), according to the degree of eggshell translucence. Translucent eggs showed thicker eggshell and lower egg yolk color. We also detected the plasma biochemical index, intestinal morphology and structure, enzyme activity, and antioxidant capacity of the hens’ producing translucent eggs and normal eggs. The results showed that the ratio of duodenal villus length to crypt depth, succinate dehydrogenase (SDH) activity, chymotrypsin, total ATPase (T-ATPase), alkaline phosphatase (AKP) and glutathione peroxidase (GSH-Px) activities were decreased in the hens produced translucent eggs (P < 0.05), but malondialdehyde (MDA) content was increased (P < 0.05); jejunal lipase activity, Na+K+-ATPase activity, total antioxidant capacity (T-AOC), GSH-Px activities were decreased (P < 0.05) in group T; ileal amylase and Ca2+Mg2+-ATPase activities were also decreased (P < 0.05) in group T. In addition, we identified a total of 471 differentially expressed genes (DEGs) in duodenal tissue, with 327 up-regulated genes and 144 down-regulated genes (|log2FC| ≥ 1 and P < 0.05). Enrichment analysis showed that the up-regulated genes, such as GSTT1, GSTO2, GSTA3, were mostly enriched in metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450 and oxidative phosphorylation pathways. The results of our study indicate that plasma lipid metabolism disorder, decreased intestinal antioxidant capacity, and altered intestinal metabolism capabilities may influence the formation of translucent eggs.

Concerns regarding the safety of ethoxyquin (EQ) have gradually increased, highlighting the necessity of identifying safer and more effective antioxidants for use in animal feed. This study investigates the effects of a compound antioxidant (CA) as an alternative to ethoxyquin on feed oxidative stability, growth performance, antioxidant capacity, and intestinal health in broilers. A total of 351 one-day-old Arbor Acres Plus male broilers were randomly assigned to three treatments with nine replicates of 13 birds each. The experimental treatments included: CON group (basal diet), EQ group (basal diet + 200 g/ton EQ at 60% purity), and CA group (basal diet + 200 g/ton compound antioxidant, which comprises 18% butylated hydroxytoluene, 3% citric acid, and 1% tertiary butylhydroquinone). The experiment lasted for 21 days. Compared to the control group, supplementation with CA significantly reduced the acid value, peroxide value, and malondialdehyde content in the feeds after storage. Moreover, CA supplementation significantly decreased feed intake and the feed conversion ratio (FCR) without affecting weight gain of boilers, while also improving liver antioxidant capacity (increased T-AOC and SOD levels), intestinal antioxidant capacity (increased CAT, HO-1, and GPX7 protein expression), and enhancing the duodenal villus height-to-crypt depth ratio and jejunal villus height. Additionally, CA treatment reduced intestinal barrier permeability (decreased diamine oxidase activity and D-lactate levels), potentially by promoting the expression of Occludin, ZO-1, and Mucin2 protein. Furthermore, the addition of CA elevated the protein levels of NF-κB p50 along with its inhibitory factors, IκB and NF-κB p105, in the intestines of broilers, thereby enhancing immune regulatory capacity. This supplementation also led to an increased abundance of beneficial gut microorganisms, including Lactobacillus, Alistipes, Candidatus Arthromitus, and Turicibacter. In comparison to the EQ group, CA supplementation enhanced feed oxidative stability, decreased the FCR, and improved the intestinal morphology, barrier functions, and inflammatory status in broilers. These findings suggest that this compound antioxidant may serve as a healthier and more effective alternative to ethoxyquin.

Recent technical advances in the stem cell field have enabled the in vitro generation of complex structures resembling whole organs termed organoids. Most of these approaches employ culture systems that allow stem cell-derived or tissue progenitor cells to self-organize into three-dimensional (3D)-structures. Since organoids can be grown from various species, organs and from patient-derived induced pluripotent stem cells, they create significant prospects for modelling development and diseases, for toxicology and drug discovery studies, and in the field of regenerative medicine. Here, we report on intestinal stem cells, organoid culture, organoid disease modeling, transplantation, current and future uses of this exciting new insight model to veterinary medicine field.

The intestinal microbial community of aquatic animals is closely related to the environment and thus affects the health of aquatic animals. Here we investigated annual variation of intestinal bacteria community structures of Ruditapes philippinarum cultured using two different methods, bottom sown and raft hanging. Bacterial diversity of seawater and sediment in different seasons was examined as well. Correlation between R. philippinarum intestinal bacteria community structures and environmental factors was analyzed. The results showed that in the two aquculture areas where R. philippinarum was differentially cultured, bacteria community structure of seawater and sediment both altered with seasons. However, neither seasonal changes nor difference in culture methods could significantly affect the intestinal bacteria community structures of R. philippinarum. Additionally, in terms of the alpha diversity of intestinal bacteria communities, there was no significant difference in R. philippinarum cultured using the two methods. For benthic cultured clams, alpha diversity of the intestinal bacterial communities was often higher than that of the environmental bacterial communities. For raft hanging cultured calms, Alpha diversity of the intestinal bacterial communities was normally comparable with that of the environmental counterparts. Beta diversity analysis showed that the intestinal bacterial community structure of R. philippinarum was mainly determined by both deterministic and stochastic processes. Correlation analysis showed that the intestinal bacterial community structures of R. philippinarum were determined by a variety of environmental factors. For clams collected from the benthic culture area, the intestinal bacterial structure was more correlated with the physicochemical properties of sediment in comparing with those of seawater. For clams collected from the raft-culture area, the intestinal bacterial structure was mainly determined by the phsicochemical characteristics of seawater. This study helps us to better understand the bacterial community structure in complex aquaculture ecosystems, providing a reference for healthy shellfish aquaculture and ecosystem protection in aquaculture area.

Perturbation in the microbial population/colony index has harmful consequences on human health. Both biological and social factors influence the composition of the gut microbiota and promote gastric diseases. Changes in the gut microbiota manifest in disease progression owing to epigenetic modification in host which influences differentiation and function of immune cells adversely. Uncontrolled use of antibiotics; chemotherapeutic drugs and change in the diet pattern usually contribute to the changes in the colony index of sensitive strains known to release microbial content in the tissue micromillieu. Ligands released from dying microbes induce TLR mimicry on interaction with TLR abnormally which skew hypoxia and sterile inflammation contributing to severity of disease like IBD autoimmunity and cancer. Various modalities/interventions practiced across the globe and future strategies for microbiota based therapeutic approaches with special emphasis on tumor and inflammatory diseases are reviewed here. Therefore the major aim and scope of this manuscript is to both discuss various modalities/interventions across the globe and to design future microbiota based therapeutic approaches for mitigating the burden with special emphasis on tumor and Inflammatory diseases.

The use of probiotics in reproductive-related dysbiosis is an area of continuous progress due to the growing interest from clinicians and patients suffering recurrent reproductive microbiota disorders. An imbalance in the natural colonization sites related to reproductive health: vaginal, cervicovaginal, endometrial and also pregnancy-related altered microbiota could play decisive role in reproductive outcomes. Oral and vaginal administrations are in continuous discussion regarding the clinical effect pursued, but probiotics as oral supplement therapy is the route administration better studied. To complement and summarise with qualitative and quantitative information of vaginal probiotics clinical studies, the main objective of this work was to retrieve the standardised protocols commonly used and their microbiota modulation capacities. The studies selected were related to treat bacterial vaginosis (BV) as the most commonly disorder, few studies on vulvovaginal candidiasis (VVC) and also administration to stabilise microbiota before in vitro fertilisation (IVF). Probiotic doses administered were similar to oral probiotics protocols, ranging from ≥ 107 CFU/day to 2.5 x 1010 CFU/day, and variable regarding posology duration from 1 day to 12 weeks, being 1 week commonly applied. Moderate modulation was achieved regarding the relative abundance decrease of abnormal microbiota, coinciding with parallel increase in Lactobacillus species.

The aim of our study was a comprehensive comparative assessment of the effect of consumption of 1 and 2% cholesterol as part of a standard diet with and without regular moderate physical activity on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. The animals were randomly divided into 5 groups according to body weight and Open Field test results: Control (n=10), 1% Chol (n=10), 2% Chol (n=10), 1% Chol + RUN (n=10) and 2% Chol + RUN. The cholesterol was additionally added in the amount of 1g or 2g/100g, respectively, to the diet of animals. The rats of experimental groups 1% Chol + RUN and 2% Chol + RUN were subjected to regular (2 days a week) physical activity on a Treadmill. In rats of four experimental groups, when compared to the Control, a response of 39 indicators was revealed. The largest number of changes in biomarkers - 29 (statistically significant, p

Long Covid has become a blight, its economic consequences overwhelming. But Long Covid (LC) may represent persistent Covid-19 in those with preexisting Candida overgrowth (CO). The features shared by both are striking. LC may be a growing subset of CO. The altered tryptophan metabolism encountered in LC is driven by IFN-γ in reaction to CO. Females are robust producers of IFN-γ, yet estrogen promotes CO.The consequent decline in serotonin and melatonin triggers the mood swings and sleeplessness respectively in LC. The low serotonin, the primary messenger in the gut brain axis, creates autonomic dysfunction. The CO induced gut dysbiosis and leaky gut initiate an autoimmune path. TNFα seen in both LC and this opportunistic yeast is at the center of the cytokine triad that leads to neurodegeneration. The Western diet, high in carbohydrates, alcohol, and glutamate, is exploited by this commensal turned parasite. Residual SARS CoV2 and Candida generate abundant ROS, inducing mitochondrial dysfunction. Alcohol tastes different for many with LC, because acetaldehyde requires functioning hepatic mitochondria. This article delves into the complex physiology and biochemistry that drive the symptoms of this conspicuous connection. Recent research has revealed innovative approaches that might address this global scourge, including D-mannose for the immune dysfunction and butyrate for the gut dysbiosis created by and seen in both LC and intestinal Candidiasis.

Codium fragile, a green algae, exhibit biological properties. In this study, we examined the effect of Codium fragile extract (CFE) on dextran sulfate sodium (DSS)-induced colitis. As the administration of CFE increased, the proliferation of Akkermansia muciniphila, which is key player in metabolic and gastrointestinal disorders, increased. After CFE administration for 10 weeks, acetic acid was revealed as the major metabolite in mouse cecum and β-glucuronidase activity in mouse feces is decreased. Further, CFE significantly alleviates the acute intestinal injury induced by DSS administration, including DAI scores and colon length. MPO activity in the colon was significantly reduced in the CFE-fed group, which indicated that CFE could inhibit neutrophils infiltration and inflammation in mice. In conclusion, a protective effect of CFE against DSS colitis suggests its clinical use for IBD patients.

Background: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing annually with a rise in the incidence of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Methods: Forty-one patients with MASH and 19 with MASH-HCC who completed survey questionnaires, underwent periodontal examinations, and subjected to sample collection (saliva, mouth-rinsed water, feces, and peripheral blood) participated in the study. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The occupancy rate of the genus Fusobacterium in the intestinal bacterial flora was significantly higher in in the MASH-HCC group than in the MASH group (p = 0.002), whereas that of Butyricicoccus (p = 0.022) and Roseburia (p < 0.05) was significantly lower. Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusion: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

Keywords: gut microbiota; small intestinal bacteria overgrowth; SIBO; diet, dysbiosis; microbial ecology.

Exogenous proteases are well established for hydrolysing proteins and improving the digestibility of amino acids, which, in animal production, enhances growth performance and diet formulation flexibility. Attention has now turned to the wider, or ‘extra-proteinaceous’, benefits of proteases. Both host and (gut) microbiome utilise amino acids for diverse functions beyond just cellular growth and proliferation. For example, the host produces a diverse array of proteinaceous secretions that seek to modulate the activity of the intestinal microbiome and opportunities to interact with host (e.g., epithelial) receptors. Reciprocally, the microbiome utilises various protein-based components to perform individual lifestyle traits, such as colonising gut niches, production of virulence traits, etc., which can be influenced by protease activity and amino acid availability. In addition, microbial fermentation of proteins and amino acids produces metabolites that may be considered undesirable (e.g., toxic) for the host’s cells or, for example, can act as signalling molecules, shaping the secretion of gut hormones and function. Parallels may also exist between various antibiotic growth promoters and proteases, in that both can target/impact microbial proteins (synthesis and degradation, respectively). There are many aspects to consider, such as determining optimal intestinal levels and spectra of proteolytic activity under various scenarios, but great potential exists.

Ingestion of corrosive agents is a well-known cause of extensive and severe gastrointestinal tract injury. Acids can result in significant acute complications throughout the gastrointestinal system. Herein, we present a case of total gastrointestinal necrosis after a patient ingested a large amount of concentrated hydrochloric acid. Of note, the patient developed an intestinal fistula six days following ingestion, requiring surgical intervention. This case underscores the potential for delayed gastrointestinal necrosis with high-volume and concentrated hydrochloric acid ingestion. Early CT evaluationto and multi-organ protectionis are crucial for such patients. For patients with no signs of perforation, multidisciplinary physicians should comprehensively evaluate the necessity of surgical exploration. In such cases, comprehensive treatment strategies can significantly improve outcomes. The purpose of this case report is to highlight the complexities and challenges in managing severe hydrochloric acid ingestion, to discuss the multidisciplinary approach required for such cases, and to contribute to the existing literature by providing detailed insights into the clinical presentation, treatment, and outcomes of a rare and severe instance of concentrated HCl ingestion.

In this study, a commercial sodium butyrate protected by a new buffer salt solution (NSB) was tested to determine whether it can be used as an antibiotic alternative in broiler production. 192 1-day-old broilers were randomly allocated to three dietary treatments: soybean meal diet (CON), antibiotic diet (ANT, basal diet + 100 mg/kg aureomycin), and NSB (basal diet + 800 mg/kg NSB). The growth performance, serum anti-inflammatory cytokines, intestinal morphology, gut barrier function, antioxidative parameters, SCFAs content, and cecal microbiota were analyzed. The result showed that NSB significantly improved ADFI, ADG (p < 0.01), and decreased FCR (p < 0.01). Serum anti-inflammatory cytokine IL-10 was up-regulated (p < 0.01), and pro-inflammatory TNF-α was down-regulated (p < 0.05) by NSB supplementation. H&E results showed that VH and VH: CD ratio significantly increased (p < 0.05) in the jejunum and ileum in the NSB group. Furthermore, ZO-1 (p < 0.01), claudin-1 (p < 0.01), and occludin (p < 0.05) in the jejunum and claudin-1 (p < 0.01) and mucin-2 (p < 0.05) in the ileum significantly up-regulated in the NSB group, respectively. Additionally, SOD (p < 0.05) and T-AOC/MDA ratio (p < 0.01) in the jejunum and SOD in the ileum were significantly increased (p < 0.05) in the NSB group. The MDA level also significantly increased (p < 0.01) in the ANT group in the jejunum. Propionic acid (p < 0.05) and butyric acid (p < 0.01) content significantly increased in the NSB group in the jejunum and ileum segments. The 16S rRNA sequencing results showed no significant difference (p > 0.05) in alpha and beta diversity among the groups. LEFSe analysis also indicated that Peptostreptococcaceae, Colidextribacter, Firmicutes, Oscillospira, and Erysipelatoclostridiaceae, which promote SCFA production (p < 0.05), were identified as dominant taxon-enriched bacterial genera in the NSB group. The Spearman correlation analysis revealed that Colidextribacter with ADFI, ADG, VH, claudin-1 (p < 0.05), and unclassified_f__Peptostreptococcaceae with ADFI, IL-10, and ZO-1 were positively correlated (p < 0.05). Furthermore, ADFI and ADG with IL-10, claudin-1, SOD, T-AOC, and butyric acid (p < 0.05), and similarly, ADG with VH (p < 0.05) showed a positive correlation. In conclusion, NSB enhanced the growth performance by improving jejunum and ileum morphology, serum anti-inflammatory cytokines, regulating intestinal barrier function and antioxidant capacity, SCFAs content, and cecum microbiota, showing its potential use as an alternative to antibiotics in poultry nutrition.

A key component of efforts to identify the biological and drug-specific aspects that contribute to therapeutic failure or unexpected exposure-associated toxicity is the study of drug-intestinal barrier interactions. While methods supporting such assessments are widely described for human therapeutics, there is relatively little information available for similar evaluation in support of veterinary pharmaceuticals. There is, therefore, a critical need to develop novel approaches for evaluating drug-gut interactions in veterinary medicine. Three-dimensional (3D) organoids can address these difficulties in a reasonably affordable system that circumvents the need for more invasive in vivo assays in live animals. However, a first step in the development of such systems is understanding organoid interactions in a 2D monolayer. Given the importance of orally administered medications for meeting the therapeutic need of companion animals, we demonstrate growth conditions under which canine colonoid-derived intestinal epithelial cells survive, mature, and differentiate into confluent cell systems with high monolayer integrity. We further examine the applicability of this canine colonoid-derived 2D model to assess the permeability of three structurally diverse, passively absorbed β-blockers (e.g., propranolol, metoprolol, and atenolol). Both absorptive and secretive apparent permeability (Papp) of these drugs at two different pH conditions were evaluated in canine colonoid-derived monolayers and were compared with that of Caco-2 cells. This proof-of-concept study provides promising preliminary results with regard to the utility of canine-derived organoid monolayers for species-specific assessments of therapeutic drug passive permeability.

Necroptosis is a caspases-independent form of programmed cell death exhibiting intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development, tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis has been associated to chronic inflammatory diseases and cancer. Drugs that inhibit necroptosis could, therefore, be used therapeutically for the treatment of these diseases, and researches to develop such inhibitors are already underway. In this Review, we outline pathways for necroptosis and its role in chronic inflammation and cancer. We also discuss current and developing therapies that target necroptosis machinery.

Pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD)-containing protein receptors (NLRs) and the pyrin and HIN domain (PYHIN) receptors initiate the inflammatory response following cell stress or pathogenic challenge. When activated some of these receptors oligomerize to form the structural backbone of a signalling platform known as the inflammasome. The inflammasome promotes the activation of caspase-1 and the maturation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the gut dysregulation of the inflammasome complex is thought to be a contributing factor in the development of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD). The importance of inflammasomes to intestinal health has been emphasized by various inflammasome deficient mice in dextran sulphate sodium (DSS) models of intestinal inflammation and by the identification of novel potential candidate genes in population based human studies. In this review we summarise the most recent finding with regard to formation, sensing and regulation of the inflammasome complex and highlight their importance in maintaining intestinal health.

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC), and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). Total 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. The 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP) were found to have difference in gene expression in intestinal- and diffuse-type GC. Total 463 direct relationships with 3 molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathways networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

The nuclear factor-ĸB (NF-ĸB) transcriptional system is a major effector pathway involved in inflammatory responses. Previous studies found that a Gardenia decoction (GD) inhibited the expression of NF-κB in a lipopolysaccharide (LPS)-stimulated mouse intestinal injury model. Herein, we hypothesized that geniposide (GE), a component of Gardenia jasminoides Ellis, also exerts anti-inflammatory effects and inhibits NF-ĸB activity in LPS-induced intestinal epithelial cells (IEC-6). IEC-6 cells were stimulated with LPS, following which the effects of GE on NF-ĸB signaling in the IEC-6 cells were examined by western blotting to detect IĸB phosphorylation/degradation. The expression of NF-κB was determined by immunofluorescence assay (IFA). Enzyme-linked immunosorbent assay (ELISA) was used to detect the inhibitory effect of GE on the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) activated by LPS in IEC-6 cells. In addition, the migration ability of IEC-6 cells was observed by the scratch method. These results showed that GE dose-dependently downregulated levels of the proinflammatory cytokines TNF-α, IL-6 and IL-1β that had been upregulated by LPS and suppressed the phosphorylation of IĸB and NF-ĸB induced by LPS. Our findings indicated that GE could reduce LPS-induced NF-ĸB signaling and proinflammatory expression in IEC-6 cells and significantly enhance the migration of IEC-6 cells. Moreover, GE inhibited the expression of NF-κB, nuclear transfer, and transcriptional activity in IEC-6 cells. GE could block the synthesis of inflammatory factors of IEC-6 cells by inhibiting activation of the IĸB/NF-κB signaling pathway induced by LPS.

Inflammatory bowel disease (IBD) is a chronic and relapsing disease caused by a dysregulated immune response to host intestinal microbiota that occurs in genetically predisposed individuals. IBD encompasses two major clinical entities: ulcerative colitis (UC), which is limited to the colonic mucosa, and Crohn disease (CD), which might affect any segment of the gastrointestinal tract. Despite the prevalence of IBD is increasing worldwide, therapy remains suboptimal, largely because the variability of causative mechanisms, raising the need to develop individualized therapeutic approaches targeted to each individual patient. In this context, patients-derived intestinal organoids represent an effective tool for advancing our understanding on IBD’ s pathogenesis. Organoid 3D culture systems offer a unique model for dissecting epithelial mechanisms involved IBDs and test individualized therapy, although the lack of a functional immune system and a microbiota, two driving components of the IBD pathogenesis, represent a major barrier for their exploitation in clinical medicine. In this review we have examined how to improve the translational utility of intestinal organoids in IBD and how co-coltures of 3D or 2D organoids and immune cells and/or intestinal microbiota might help to overcome these limitations.

Vaginal ecosystem is a unique environment where, in physiological conditions, lactobacilli dominate. However, also pathogenic microbial species, responsible of vaginitis and vaginosis, can harbor vaginal microbiota. To extend the data published by De Seta and Larsen in Pathogens (2021), here we analyzed both the anti-Candida and anti-inflammatory properties of the vaginal gel formulation, Respecta® Balance Gel (RBG), commercialized as an adjuvant to treat vaginitis and vaginosis. We evaluated its activity by an in vitro model where a monolayer of A-431 vaginal epithelial cells was infected by Candida albicans in the presence of RBG or the placebo formulation (pRBG). Specifically, we tested the RBG capacity to counteract C. albicans virulence factors as well as their anti-inflammatory properties. Our results show that, unlike the placebo, RBG reduces ,reduces, C. albicans adhesion, its capacity to form hyphae and C. albicans-induced vaginal cell damage. Interestingly, both RBG and pRBG reduce LPS-induced IL-8 secretion (being RBG the most effective) demonstrating that also the placebo retains anti-inflammatory properties. By our experimental approach we highlight the possible role of farnesol on such effects, but we would like to point out that lactic acid, polydextrose and glycogen too must be relevant in the actual application. Taken together, our results show that RBG impairs C. albicans virulence and is able to reduce the inflammation in the vaginal environment, ultimately allowing the establishment of a balanced vaginal ecosystem.

The causal networks are important for understanding the signaling alterations in diseases. To reveal the network pathways affected in epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs), which are related to poor prognosis of cancer, the molecular networks and gene expression in diffuse- and intestinal-type gastric cancer (GC) have been analyzed. The network pathways in GC were analyzed in Ingenuity Pathway Analysis (IPA). The analysis of the probe sets of which gene expression has significant differences between diffuse- and intestinal-type GC in RNA Sequencing publicly available data identified 1099 causal networks in diffuse- and intestinal-type GC. Master regulators of the causal networks included lenvatinib, pyrotinib, histone deacetylase 1 (HDAC1), mir-196, and erb-b2 receptor tyrosine kinase 2 (ERBB2). The analysis of the HDAC1-interacting network identified the involvement of regulation of EMT by growth factors pathway, coronavirus pathogenesis pathway, and vorinostat. The network had RNA-RNA interactions with microRNAs such as mir-10, mir-15, mir-17, mir-19, mir-21, mir-217, mir-223, mir-25, mir-27, and mir-34. These molecular networks revealed in the study may lead to the identification of drug targets for GC.

With the development of social economy, the quality of national life has been rapidly improved, along with the accelerated aging of the population and the continued prevalence of metabolic risk factors. Cardiometabolic diseases (CMDs) have become a major disease burden for both urban and rural residents in China, and most of them are related to lifestyle changes in modern society, especially circadian rhythm disorders. Circadian rhythm regulating the activity of metabolism, such as carbohydrates, lipids, and other nutrients, is the most important pathway modulating the health. Nowadays, studies have shown that the interaction between circadian rhythmicity and gut microbiota counts for the homeostasis of metabolic health, while circadian rhythm disruption is associated with gut microbiota dysbiosis and metabolic diseases. However, there is a lack of research on the topic of gut microbiota mechanisms regulating circadian rhythm disruption leading to CMDs. With increased burden of CMDs prevention and treatment, as well as the demand of healthcare resource allocation, it prompts us to put forward a new strategy to solve this problem. This review focuses on the interactions between circadian rhythm and gut microbiota to elucidate the potential mechanisms of circadian rhythm disruption induced CMDs, providing a solid support for further prevention and treatment.

Probiotics have emerged as a prominent alternative to antibiotics in antimicrobial-free broiler farming. To assess the effect of the probiotics Sphingomonas sp. Z392 isolated and identified by this this laboratory on broiler growth, we conducted a study to examine the changes in broiler body weight, EPI, intestinal histological structure and gut microbiota. The results showed that supplementation of broiler drinking water with 4 × 105 CFU/mL of Sphingomonas resulted in an increase in the relative abundance of Lactobacillus, Bacteroides, Lachnospiraceae, Aminobacterium, Oribacterium, Christensenellaceae, Faecalibacterium, Barnesiella, Ruminococcus, Parabacteroides, Phascolarctobacterium, Butyricicoccaceae, and Caproiciproducens, which were reported to be positively correlated with the digestion and absorption of broiler chickens. The relative abundance was increased of Odoribacter, Alistipes, Parabacteroides, and Rikenellaceae, which were reported to be negatively correlated with the occurrence of intestinal diseases. The relative abundance was decreased of Campylobacter, Shigella Castellani, Bilophila, Campylobacter, Clostridia, and Anaerotruncus, which were reported positively correlated with the occurrence of intestinal diseases. At the same time, it was increased in the integrity of small intestinal villus morphology, the number of goblet cells in small intestinal epithelial cells, the health of mitochondria in the cytoplasm of jejunal villous epithelial cells, and the number of lysosomes in the cytoplasm of goblet cells in small intestinal epithelium, ileal villous epithelial cells, mitochondria in the cytoplasm of large intestinal villous epithelial cells, the VH/CD of the ileum, digestive, absorption, and defense capabilities. Especially the final weight was increased by 4.33% and the EPI increased by 10.10%. Therefore, the supplementation of broiler drinking water with Sphingomonas generated better economic benefits for the broiler chickens.

A prospective longitudinal study of 54 patients who underwent intestinal anastomosis and were started on early enteral nutrition at the University Hospital of the Central University of Venezuela (November 2022 to September 2023), all of them fulfilled the inclusion criteria. Taking as early enteral nutrition two study groups: GROUP 1 tolerance at 24 hours and GROUP 2. Tolerance at 48 hours. Hospital stay and complications were evaluated. Of the 54 patients 40(74.1%) were operated on in emergency surgery 46(85.2%) patients were male. There was no difference in the mean ages of the two diet groups (P=0.254), the mean age was 33.9/14.8 years. There was no statistically significant difference (P=0.086) in the mean number of days of hospitalization (4.7/2.4 days) between patients according to the type of diet. Vomiting occurred in 20.37%, with no statistically significant differences between the groups of patients with diet 1 and 2. There were 2 (3.7%) cases of leakage that required reintervention, and this complication was not associated with the initiation of a particular type of diet, type of surgery, surgical time or site of injury. Early enteral nutrition is a viable option in patients undergoing intestinal anastomosis, is not associated with the incidence of dehiscence, is well tolerated by the patients, has acceptable complications, most frequently associated with vomiting, and reduces hospital stay.

Radiosensitivity, the susceptibility of cells to ionizing radiation, plays a critical role in understanding the effects of radiation therapy and exposure on tissue health and regeneration. Identifying characteristics that predict how a patient may respond to radiotherapy enables clinicians to maximize the therapeutic window. Limited clinical data suggested a difference in male and female radiotherapy outcomes. Radiotherapy for gastrointestinal malignancy is still a challenge due to intestinal sensitivity to radiation toxicity. In this manuscript we demonstrated sex specific differences in intestinal epithelial radiosensitivity. In mice model of abdominal irradiation, we observed significant increase in oxidative stress and injury in male compared to female. Lgr5+ve intestinal stem cells from male mice showed higher sensitivity to radiation induced toxicity. However, sex specific differences in intestinal radiosensitivity are not dependent on sex hormone as we demonstrated similar sex specific radiosensitivity differences in pediatric mice. In ex-vivo study we found that human patient derived intestinal organoid (PID) derived from male showed higher sensitivity to irradiation compared to female as evident from loss of budding crypt, organoid size, and membrane integrity. Transcriptomic analysis of human Lgr5+ intestinal stem cells suggested radiation induced upregulation of mitochondrial oxidative metabolism in male compared to female possible mechanism for radiosensitivity differences.

Intestinal gases are usually discarded as physiologically inert, useless sub-products of colonic fermentation that must be expelled to prevent discomfort and meteorism. Starting from the observation that many living beings use exogenous and/or endogenous gases to attain evolutionary benefits, we question whether intestinal gases in healthy humans could have underestimated physiological effects, either intestinal or extra-intestinal. We examine gaseous volume, composition, source and local distribution in proximal as well as distal gut, providing extensive data that may serve as reference for future studies. We analyze each one of the most abundant intestinal gases and describe their diffusive patterns, active trans-barrier transport dynamics, chemical properties, intra-/extra-intestinal metabolic effects mediated by intracellular, extracellular, paracrine and distant actions. Discussing the physical properties of the whole intestinal gaseous mixture, we illustrate how changes in volume/pressure can be generated by two different mechanisms, namely, physical muscular gut contraction and biological colonic fermentation, with quite different metabolic outcomes. The experimental gas laws suggest that the gaseous exchanges between lumen and bloodstream are impaired by muscular contraction and improved by muscular relaxation. In turn, the surface-area-to-volume ratio suggests that the gaseous exchanges are impaired by microorganismal overproduction and improved by microorganismal reduction. Further, theoretical stochastic approaches from probability theory indicate that the non-turbulent, random paths of gas molecules inside colonic haustra do not homogenously spread over the whole mucosal surface. This means that the intestinal area available for lumen/blood metabolic exchanges is much less than expected not just in disease states, but also in healthy individuals.

Both lactic acid and short chain fatty acid (SCFA) play important roles in maintenance of intestinal epithelial structure and function. Trilactic glyceride (TLG) obtains both excellences of lactic acid and SCFA. This study was to investigate the effects of trilactic glyceride on growth performance, blood parameters, liver function, intestinal morphology and intestine function of piglets. Twelve weaned piglets (21±2 d) were randomly allocated to two treatment groups: 1) control group, piglets fed the basal diet; 2) TLG group, piglets fed the basal diet supplemented with 0.5 % TLG. On day 21 of the trial, D-xylose (0.1 g/kg·BW) was orally administrated to all piglets and blood samples were collected 1 h thereafter. Then, all the piglets were sacrificed to examine intestinal mucosal morphology and collect fatty tissue, liver and intestinal mucosa for further analysis. The results showed that: compared with the control group, TLG group decreased blood ALB and GGT on day 10 and 20, TLG group decreased blood TP and increased blood TG on day 20 of the trail (p < 0.05); TLG group decreased blood D-xylose and LDL, increased blood HDL (p < 0.05). These data suggested that supplementing trilactic glyceride had beneficial impacts on promoting nutrients’ metabolism, maintaining intestinal integrity, and alleviating oxidative stress and diarrhoea. Further research of molecular mechanisms showed changing expression levels of related proteins and genes, suggesting that these could be involved in the regulation of the impact. The community composition of the gut microbiota was also found to be altered in several operational taxonomic units within the genus, Prevotella (order Bacteroidales), and the order, Clostridiales.

Image processing is a field of which its popularity increases and continues and, that grows dynamically with new technologies. Nowadays, image processing finds itself in use in almost every field. One of these uses is undoubtedly in the field of medicine, where diagnosis and treatment planning are made from images and, which is constantly changing with newly developed techniques. Of course, the most important factor in using this so widely in the medical field is the acquisition of images on every medical field. With the help of these images, the complaints can be seen more easily and the doctor can follow a path in the treatment of the disease. In our study, we used the Region Growing segmentation method to detect the intestinal mass. This study compares the area determined by the specialist with the area obtained with the segmentation process and, it is seen that the created software system can be used as an auxiliary system to specialist doctors.

Circadian rhythm disruption is increasingly considered an environmental risk factor for the development and exacerbation of inflammatory bowel disease. We have reported in a previous study that nychthemeral dysregulation is associated with an increase in intestinal barrier permeability and inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. To investigate the effect of circadian rhythm disruption on the composition and diversity of the gut microbiota (GM). Sixty male C57BL/6J mice were divided initially to two groups, the shifted group (n=30) exposed to circadian shifts for three months and the non-shifted group (n=30) under a normal light-dark cycle. The mice of the shifted group were cyclically housed for five days under the normal 12:12 hour light-dark cycle followed by another five days under reversed light-dark cycle. At the end of the three months a colitis was induced by 2 % DSS given in the drinking water of 30 mice. Animals were then divided into four groups (n=15 per group), sham group non-shifted (Sham-NS), sham group shifted (Sham-S) and DSS non-shifted (DSS-NS) and DSS shifted (DSS-S). Fecal samples were collected from rectal content to investigate changes in GM composition by DNA extraction followed by high-throughput sequencing of the bacterial 16S rRNA gene. The mouse GM was dominated by three phyla: Firmicutes, Bacteroidetes and Actinobacteria. The Firmicutes/Bacteroidetes ratio decreased in mice with induced colitis. The richness and diversity of the GM were reduced in the colitis group, especially in the group with inverted circadian rhythm. Moreover, GM composition was also modified in the inverted circadian rhythm group, with an increase in Alloprevotella, Turicibacter, Bacteroides and Streptococcus genera. Circadian rhythm inversion exacerbates GM dysbiosis to a less rich and diversified extent in a DSS-induced colitis model. These findings shows a possible interplay between circadian rhythm disruption, GM dynamics, and colitis pathogenesis.

Aim: To analyze a single center's experience with Short Bowel Syndrome/ Chronic Intestinal Failure (SBS/CIF) in adult patients treated with Home Parenteral Nutrition (HPN). Materials and methods: In the last thirty years, 13 patients with SBS/CIF were included in an HPN program. Results: Between 1992 and 2023, 13 patients were included in an HPN program. The primary underlying pathology was acute mesenteric ischemia. The median age of the starting HPN was 44 years old. Most are submitted to several surgeries of extensive intestinal resection with posterior intestinal reconstruction. Five of the 13 patients have died while on HPN for a median of 42 months. The causes of death HPN-related were catheter sepsis, endocarditis with cardiac failure, or hepatic failure. One patient died due to underlying pathology: pelvic abscesses and bleeding related to radiotherapy. Eight patients remain alive with a median time of HPN of 173 months. During the HPN support, the most frequent complications were venous catheter infection and venous territory thrombosis. None of the eight patients alive have hepatic failure. Two patients recently started teduglutide, with good tolerance, and need reduction of HPN support. All these eight patients have a satisfactory quality of life (parenteral support needs range between five to two nutrition bags per week). Conclusion: HPN remains the gold standard of SBS/CIF treatment, although Teduglutide may reduce HPN needs and HPN complications and provide a better quality of life. An HPN multidisciplinary healthcare group support is essential to ensure these patients' survival and quality of life. Keywords Short bowel Syndrome, Chronic Intestinal failure, Home Parenteral Nutrition, Teduglutide, Complications of Parenteral Support.

In the past decade, it has been discovered that intestinal flora can influence various organ-specific cancers by altering the body's energy balance, increasing obesity, synthesizing genetic toxins and small signaling molecules, initiating and modulating immune responses, and metabolizing indigestible dietary components, exogenous substances, and drugs. In this review, we will focus on elucidating the role of gut flora based on its molecular mechanisms and its potential therapeutic implications in head and neck tumors in the near future.

Increased sugar intake is implicated in Type-2 diabetes and fatty liver disease. Mechanisms by which glucose and fructose components promote these conditions are unclear. We hypothesize that alterations in intestinal metabolite and microbiota profiles specific to each monosaccharide are involved. Two groups of six adult C57BL/6 mice were fed for 10-weeks with a diet where either glucose or fructose was the sole carbohydrate component (G and F, respectively). A third group was fed with normal chow (N). Fecal metabolites were profiled every 2-weeks by ¹H NMR and microbial composition was analysed by real-time PCR (qPCR). Glucose tolerance was also periodically assessed. N, G and F mice had similar weight gains and glucose tolerance. Multivariate analysis of NMR profiles indicated that F mice were separated from both N and G, with decreased butyrate and glutamate and increased fructose, succinate, taurine, tyrosine and xylose. Compared to N and G, F mice showed a shift in microbe populations from gram-positive Lactobacillus spp. to gram-negative Enterobacteria species. Substitution of normal chow carbohydrate mixture by either pure glucose or fructose for 10 weeks did not alter adiposity or glucose tolerance. However, F G and N mice generated distinctive fecal metabolite signatures with incomplete fructose absorption as a dominant feature of F mice.

To explore the effect of lily polysaccharide (LP) on immune function and intestinal flora in immunosuppressive mice.The immunosuppressive model was established by intraperitoneal injection of cyclophosphamide (CTX) in mice, and the immunological indexes were measured. The cecal contents of mice were taken, and the DNA of intestinal flora was extracted for 16S DNA sequence analysis.Compared with CTX group, the body weight and thymus index of mice in each treatment group increased significantly, the liver index decreased significantly,the hepatocyte morphology, liver plate and hepatic sinus arrangement of mice in high and low concentration LP groups were relieved in varying degrees, and the contents of IgA and IgG in serum of mice in low concentration LP group and positive control group increased significantly; The contents of TNF-α and IL-6 in colon decreased, while the contents of IL-10 increased significantly. The contents of AST, ALT and MDA in liver decreased significantly, while the content of SOD increased significantly. Compared with the blank group, LP can improve the intestinal flora of immunosuppressive mice , mainly by increasing the abundance of beneficial bacteria such as s24-7, Bacteroides and butyrimionas and reducing the abundance of harmful bacteria such as Prevotella, dorea and adlercreutzia.

Intestinal parasitic infections pose a grave threat to human health, particularly in tropical and subtropical regions. The traditional manual microscopy system of intestinal parasites detection remains the golden standard procedure for the diagnosis of parasites cyst or eggs, but this approach is costly time-consuming (30min/sample), highly tedious, and also required specialist. However, computer vision based on deep learning has made great stride in recent time. Despite the significant advances in deep convolutional neural network-based architectures, little research has been conducted to explore the potential of these techniques in the field of parasitology, specifically for intestinal parasites. Therefore, the goal of this research is to evaluate the performance of proposed state-of-the-art transfer learning architecture for detecting and classifying intestinal parasite eggs from images. We would ensure that patients receive prompt treatment while also relieving experts of extra work if we used such an architecture. Here, in stage first, we applied image pre-processing and augmentation to the dataset, and in stage second, we utilized the YOLOv5 algorithms for detection and classification and then compared their performance based on different parameters. Our algorithms achieved a mean average precision of 97% approximatiely and 8.5 ms detection time per sample for 5,393 intestinal parasite images. Thus, this approach may form a solid theoretical basis for real-time detection and classification in routine clinical examinations while accelerating the process to satisfy increasing demand.

β-glucan is a generic term for insoluble dietary fibers exerting various effects on the immune system. As a group, β-glucans are non-cellulose polysaccharides composed of a glucopyranose as the main constituent sugar with β configuration, having a β- (1,3)-linked glucopyranose main chain as a common feature. β-glucans are absorbed through the intestine. Since the 1980s, there have been many studies reporting various effects of β-glucans on the immune system, including reports on receptors, that have slowly clarified their recognition system and action mechanisms. However, these studies focused mostly on treatments of infectious diseases and tumors; thus, the effects of β-glucans ingested in food as dietary fiber and their mechanisms of action remain largely unknown. The uptake of β-glucan into the body may be resemble that of proteins, which are soluble polymers, and insoluble material such as dietary fiber. Dietary fibers have varied structures, with wide-ranging solubility and physiological effects. Understanding whether these substances are actually taken up, how they exert their effects, and their metabolism after being taken up are important issues when considering the functionality and safety of dietary fibers.

Human intestinal flora refers to a large and diverse microbial population present in the digestive tract of the human body, which plays a significant role in the establishment of human immune homeostasis and the normal function of the immune system. Myasthenia Gravis is an autoimmune disease of the neuromuscular junction, mainly involved in the anti-acetylcholine receptor antibody, cellular immune dependence, and complement¹. At present, studies have found that the intestinal flora of Myasthenia Gravis is different from that of healthy people. Probiotic therapy has been shown effective in the experimental autoimmune Myasthenia Gravis animal models. This article reviews the relationship between intestinal flora and Myasthenia Gravis, to provide new ideas for further study of the pathogenesis and clinical treatment of Myasthenia Gravis.

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal0 tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e. g. vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α, 25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g. butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD /VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

Abstract: Gastroesophageal reflux disease (GERD), the inflammatory bowel disease (IBD), and mental health issues are significant public health concerns in globally. Although rising peaks observed post-COVID-19, there is a sever paucity in high quality data. Using descriptive analysis, we identified the frequency and associations of age- and gender, sport, genetic, and psychiatric consequences in the coexistence of GERD and IBD in 2067 participants 18 to &gt;60 years with mean age of 26.8 ± 12.9 years. Most were 18 -29 years old (66%, n=1364) of which majority were young Saudi females (72.4%, n=1496). Estimated 1099 (53.2%) were students, 428 (20.7%) were unemployed, and 540 (26.1%) were. The majority were Saudis (94.7%, n= 1957). Psychological syndromes anxiety (60.7%), stress (60.7%), and depression (60.6%) were most frequent; whereas, IBD (48.7%) and GERD (36.3%), respectively were the second and third. In 51 % respondents depression, anxiety, and stress occurred first while in 33.9%, and 24.3% IBD and GERD, respectively, were the first signs. In most respondents (59.2%, n=1178), these signs first appeared recently and 33.6% (n=669) reported occurrence during adult life, and only in 7.2% (n=144) the signs noticed during childhood (7.2%, n=144)). Aggravating factors were 32.9% (n=681) genetic and other factors of which 476 (69.9%) inherited IBD while 215(31.6%) and 175 ((25.7), respectively, inherited psychological (depression, anxiety, and stress) and GERD. However, only 18.3% sought treatment (n=378) and only 66 (3.2%) had colectomy or a colostomy bag. Little over half of the studied population (58.1%, n=1201) were active in outdoor. GERD or IBS and psychological factors (anxiety, depression, and stress), were significantly associated with age (P value =.001).; GERD with old age, IBD with mid-age 40-49 years, and psychological disorders among younger ages. Thus, while mental health issues predispose young millennial women to neurogastroenterological disorders, the IBD and GERD initiate psychological problems in old and mid-ages, respectively. Intriguingly, despite the significantly mosaic global genetic population structures, their lifestyles, and nutritional habits, the pattern of these disorders remains similar. Thus, this is potentially consistent with notion that the gut nerve cells are conserved and that the changes in gut dysbiosis of gut microbiome signatures are responsible. These findings have significant clinical implications in the patient treatment strategies and tailored educational and awareness programs in lifestyle medicine. Future microbiome studies would reveal more insight into the mechanisms of disorders.

Bile acids (BAs) play a crucial role in the human body's defense against infections caused by bacteria, fungi, and viruses. BAs counteract infections not only through interactions with intestinal bacteria exhibiting bile salt hydrolases (BSHs) activity but also directly combat infections. Building upon our research group's previous discoveries highlighting the role of BAs in combating infections, we have initiated an in-depth investigation into the interactions between BAs and microbiota. Leveraging existing literature, we offer a comprehensive analysis of the relationships between BAs and 16 key microbiota. This investigation encompasses bacteria (e.g., Clostridioides difficile, Staphylococcus aureus, Escherichia coli, Enterococcus, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Bacteroides, Clostridium scindens, Streptococcus thermophilus, Saccharomyces boulardii, Clostridium butyricum, Lactic Acid Bacteria), fungi (e.g., Candida albicans), and viruses (e.g., Coronavirus SARS-CoV-2, influenza virus, norovirus). Our research underscores the critical role of the interplay between BAs and intestinal microbiota, including Bacteroides, Clostridium scindens, Streptococcus thermophilus, Saccharomyces boulardii, Clostridium butyricum, and Lactic Acid Bacteria, in maintaining intestinal homeostasis and combating infections. It is imperative to note that Primary bile acid (PBA) and Secondary bile acid (SBA) often exhibit distinct roles in the anti-infection process. In the antimicrobial action of BAs, SBA demonstrate antagonistic properties against a wide range of microbiota, with the exception of Norovirus. Given the intricate interplay between BAs and intestinal microbiota, and their regulatory effects on infections, we assert that BAs hold significant potential as a novel approach for preventing and treating intestinal microbial infections.

Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer Disease will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed focussing on Alzheimer Disease pathogenesis.

The study assessed the impact of different diets on gastrointestinal pH, intestinal microbiota, digestive tract morphometry, and productive performance in guinea pigs. A total of 160 improved genotype guinea pigs were used, distributed into three groups with different diets: alfalfa (T1), alfalfa + concentrate (T2), and concentrate (T3), to which a mixture of probiotics combined with vitamins, minerals was added and amino acids in T2 and T3. Gastrointestinal pH showed significant differences between treatments in the various segments of the digestive tract. The intestinal microbiota varied according to the diet, with Escherichia coli being the predominant bacterium in weaned guinea pigs. Intestinal morphometry was significantly altered with the addition of a reinforced probiotic mixture, improving the length and density of intestinal villi. Productive parameters such as weight gain, feed consumption, and feed conversion were better in guinea pigs fed a mixed diet with 0.5% probiotic mixture. These results indicate that intestinal pH may influence microbial composition, which impacts productive efficiency and immune health, highlighting the importance of balanced nutrition and supplementation to optimize the health and performance of guinea pigs.

Objective: To investigate the causal relationships between intestinal microbiome biomarkers and colorectal cancer (CRC) and its subtypes. Method: The meta-analysis method was used to integrate the largest genome-wide association study data from the MiBioGen consortium (n=18,340). Single nucleotide polymorphisms (SNPs) significantly associated with intestinal microbial relative abundance were extracted as instrumental variables (IVs). Based on the Finnish database (R9 version) with 326,322 participants, the two-sample Mendelian randomization (MR) analysis was adopted to explore the causal relationships between intestinal microbes and CRC and its specific subtypes, such as colon cancer and rectal cancer. Result: A total of 3,310 SNPs were screened as IVs. The MR analysis revealed significant associations between various microbial traits and CRC, including its subtypes. Specific microbes, such as Erysipelotrichaceae, exhibited protective effects, while others, like Orato, were demonstrated as risk factors. Notably, specific biomarkers (e.g., Streptococcus thermophilus) for CRC were determined. This study provides new insights and potential targets for the pathogenesis, diagnosis, and treatment of CRC. Conclusion: Significant causal relationships exist between intestinal microbes and CRC and its pathological types. Specific microbes, such as Erysipelotrichaceae, play a protective role, whereas others, like Orato, serve as risk factors. These findings offer new insights into the pathogenesis of CRC and provide a foundation for future prevention and treatment strategies.

Background: Hereditary Hemorrhagic Telangiectasia (HHT) is a vascular autosomically inherited rare disease. Epistaxis (nose bleeds) is the most common symptom in HHT, leading to anemia and affecting patient’s quality of life. In addition to epistaxis, gastrointestinal bleeding (GI), more often at older ages, may lead to severe anemia and need for blood transfussions. Thus, finding drugs to control both types of bleeding is a primary necessity in HHT. Methods: A cross-sectional observational study was conducted in a series of 11 HHT patients treated with low tacrolimus doses (0.5-1mg) on an off-label prescription basis. Patients showed refractory bleeding to previous treatments. Epistaxis severity score (ESS) and hemoglobin levels were parameters used to evaluate tacrolimus impact. The occurrence of side effects was also recorded. Results: Tacrolimus was well tolerated in most of the patients, except in 2 which abandoned the treatment. The remaining patients tolerated the treatment, with a general improvement in their health condition. Epistaxis was significantly reduced comparing the ESS before and after treatment. Hemoglobin levels were significantly increased overcoming the anemia in the course of the treatment. Conclusion: Tacrolimus at low doses should be considered as a promising treatment for bleeding derived of epistaxis and GI in HHT.

Immune-mediated bowel diseases (IMBD), including Ulcerative colitis and Crohn's disease, represent a significant global health burden with their complex etiology and increasing prevalence. The connection between intestinal parasites and the gut microbiome in immune-mediated bowel disease is a complex and evolving field of research. Several studies have demonstrated that intestinal parasites can modulate the composition and function of the gut microbiome. Parasitic infections can result in alterations in the gut microbial community, including changes in microbial diversity, abundance, and metabolic activity. These changes can influence the immune response and contribute to the development of IMBDs. In contrast, the gut microbiome serves a pivotal function in maintaining intestinal homeostasis and immune regulation. Dysbiosis, characterized by changes in the gut microbial composition, has been associated with the pathogenesis of IMBDs. Imbalances in the gut microbiota can result in increased gut permeability, chronic inflammation, and aberrant immune responses, all of which are hallmarks of IMBDs. The bidirectional interaction between intestinal parasites and the gut microbiome further complicates the understanding of immune-mediated bowel diseases. Certain parasites, such as hookworms and Necator americanus, have been found to downregulate immune responses and may have therapeutic potential in treating celiac disease. On the other hand, infections with parasites like Strongyloides stercoralis and Blastocystis have been shown to mimic the symptoms of IBD, highlighting the intricate relationship between parasites and the pathogenesis of these diseases. Additional investigation is required to comprehensively elucidate the mechanisms that underlie the association between intestinal parasites and the gut microbiome in immune-mediated bowel disease. This knowledge could potentially lead to the development of targeted therapeutic strategies that aim to restore gut microbiota homeostasis and alleviate the symptoms of these debilitating conditions. By understanding and harnessing the complex interplay between parasites, the gut microbiome, and the host immune system, researchers may uncover novel approaches for the management and treatment of immune-mediated bowel diseases.

The purpose of this study was to see how dietary supplementation with phenylpyruvate affected broiler chicken growth, slaughter performance, gut health microbiota, and immunity. A total of 288 day old broiler chickens were randomly assigned to one of four groups (6 replicates each with 12 chicken). NC (basal diet), PC (basal diet plus antibiotic virginiamycin 15ppm), LCP and HCP (basal diet plus phenylpyruvate 1kg/t and 2kg/t, respectively). Results showed that PC had higher ADFI during the first 21 days, and better FCR than the NC, the LCP and HCP also improved broilers’ FCR 0.001 and 0.037% in relation to NC respectively. HCP has a higher all-eviscerated ratio than NC and less abdominal fat than LCP. HCP has increased villus length and crypt depth in the ileum compared to the NC. Bursa was lower in HCP and thymus was lower in LCP and PC. In contrast HCP have lower pro-inflammatory cytokine IL-1, as well as lower TLR4. The phenylpyruvate improved family Selenomonadaceae, genus Megamonas Bacteroides species that are known for beneficial effects like for maintenance of the cell surface structure, regulating aromatic amino acids and C. jejuni-suppressive treatment respectively. Finally, phenylpyruvate feed supplement can be utilized to improve growth performance and positively modulate gut microbiota, however this is less efficient than antibiotics in improving growth performance, although more efficient in improving productive performance and gut morphology. Moreover, high dose of phenylpyruvate is more effective than low dose

Probiotics are namely yeast and bacteria which are regarded as dietary supplements and food. Many probiotics are being commonly used now, the most frequently used, lactic acid bacteria are called Lactobacillus and Bifidobacterium. Many of the diseases associated with GIT are related to microbiota found in GIT, an imbalance of which causes gastrointestinal diseases. Probiotics, in light of scientific literature, are thought to play an important role in relieving symptoms of many diseases associated with GIT, i.e. beneficially regulating the microbiota composition. In the present review, we aimed to highlight the main considerations for main probiotic formulations to date. This study reviews the role of different probiotic formulations introduced so far in treating GI diseases in cohort ageing ≤18 years. We searched PubMed and Clinicaltrials.gov without any restrictions. This study comprises the descriptive and comparative analysis between Single-organism and Composite probiotics. These GI diseases include NEC, FAP, AGE, Acute Diarrhea, Ulcerative Colitis and etc. The results have been categorized according to title and outcomes. The positive outcomes emphasize the drug’s effectiveness in improving health and the negative outcome elaborates on the adverse effects the drug may have shown. Conclusively, discussed practices will assist in reducing GI disorders and strengthening the gut. Further insight into the various gut microbes and microbiomes with specific demographic is recommended.

Purpose: To assess the clinical safety and possible effectiveness of Vasoactive Intestinal Peptide in the treatment of Acute Respiratory Distress Syndrome (ARDS) related to sepsis. Methods: Under FDA Investigational New Drug clearance, 8 patients with ARDS related to sepsis were treated with 50 pmole/kg/hr – 100 pmole/kg/hr of Vasoactive Intestinal Peptide by intravenous infusion for 12 hours. All patients were on mechanical ventilation and full telemetery. Results: No drug-related serious adverse events were seen. Hypotension was seen in association with two infusions and diarrhea in association with one, but did not necessitate cessation of therapy. Bigeminy was seen in association with one infusion without sequelae. Seven of eight patients demonstrated a successful course during intensive care and were successfully removed from mechanical ventilation and discharged from intensive care. The eighth patient succumbed to purulent secretions in the lungs. Of those who were discharged from the ICU, six demonstrated successful 30 day survival. The seventh died from a cerebral infract at day 30, deemed unrelated to treatment with VIP. Serum levels of Tumor Necrosis Factor α were obtained in 6 patients at baseline and 24 hours and were seen to decrease with treatment in five patients. Conclusions: Initial clinical results of treatment with VIP in patients with ARDS demonstrated a safety profile consistent with previous studies in normal volunteers. The successful clinical course seen in 7 of 8 patients in the setting of an expected 50% survival may suggest that VIP shows promise in the treatment of other infectious conditions that damage the pulmonary epithelium, particularly COVID-19.

Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria, and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.

Epithelial-mesenchymal transition (EMT) networks are essential in acquiring the drug resistance and cancer malignant features in cancer stem cells (CSCs). In this regard, gene expression profiles in diffuse- and intestinal-type gastric cancer (GC) have been analyzed to reveal the network pathways in EMT and CSCs, since the diffuse-type GC has much more mesenchymal features than intestinal-type GC that has the intestinal features. The study results revealed that the activation state of several canonical pathways related to cell cycle regulation was altered. The canonical pathway on Cell cycle: G1/S checkpoint regulation was activated in diffuse-type GC, and canonical pathways on Cell cycle control of chromosomal replication and Cyclins and cell cycle regulation were activated in intestinal-type GC. Canonical pathway related to Role of BRCA1 in DNA damage response was activated in intestinal-type GC, where BRCA1, which is related to G1/S phase transition was up-regulated in intestinal-type GC. Several microRNAs (miRNAs), including mir-10, mir-17, mir-19, mir-194, mir-224, mir-25, mir-34, mir-451, and mir-605, were identified to have direct relationships of RNA-RNA interaction in Cell cycle: G1/S checkpoint regulation pathway. Additionally, cell cycle regulation may be altered in EMT conditions. The alterations in activation states of the pathways related to cell cycle regulation in diffuse- and intestinal-type GC would indicate the significance of cell cycle regulation in EMT.

Regulation of the diet in terms of the content of soluble and insoluble fibre is of great importance from the point of view of dietetics, microbiology of the gastrointestinal tract and immunology of the organism. Dietary fibre plays an important role in maintaining the balance between the con-tinuity of gut mucus production (intestinal mucosa), the stability of the intestinal microbiome composition, the regeneration of the intestinal epithelium and the immune status within the gut-associated lymphoid tissue (GALT) are played by pectin and their metabolic products in the form of pectin oligosaccharides. The main purpose of this review was to focus on pectin, their functions, their impact on the human's health and on some of the most promising prebiotics due to their solubility in the gastrointestinal tract in the form of pectin oligosaccharides. They have the properties of pectin, but have also additional features and postbiotics obtained in fermentation process can affect the intestinal microbiome and GALT-related immunity. They can be obtained from plant agro-wastes.

Bowel intussusception is a rare cause of acute or subacute abdomen in adults. The frequency, etiology, symptoms, diagnosis and treatment of the disease differ significantly in comparison to the pediatric population. In adult patients, the cause of the intussusception in the majority of the cases is an underlying intestinal tumor (benign or malign), leading in a complete or incomplete mechanical ileus with corresponding symptoms. Diagnosis via imaging modalities may be challenging and is sometimes set only after exploratory laparotomy. Surgical treatment in adult patients is most of the times mandatory, because it aims not only to reverse the intussusception but also to treat the underlying cause of the disease. We present 4 cases of adult intussusception that were treated surgically and discuss the crucial points in the management of this disease through a review of the literature.

Gastrointestinal diseases caused by parasites are frequently diagnosed in the clinical routine of domestic animals, especially dogs and cats. In general, they trigger factors that can affect individual health due to zoonoses. Therefore, this study aims to identify the main intestinal parasites obtained from the fecal samples of dogs and cats in the municipality of Jata, Brazil, and their associated risk factors. Between October 2020 and March 2022, fecal samples were collected from 359 dogs and 55 cats through spontaneous defecation and subsequently subjected to coproparasitological analyses using the Willis fluctuation and Hoffman spontaneous sedimentation techniques. The following parasitic species were identified: Ancylostoma, Toxocara, Trichuris vulpis, Dipylidium caninum; Giardia, Entamoeba, Cystoisospora, and Platynosomum fastosum. The risk factors associated with parasitism include age, average income of owners, access to garbage, sewage, waste, outdated deworming, and contact with animals. The results demonstrate the need to establish public policies and implement preventive and control measures to reduce the occurrence of parasites in animals and the exposure of humans to pathogenic agents.

We previously showed that, based on the frequency and distribution of specific cell types, rainbow trout (RT) intestinal mucosa is divided in two regions that form a complex nonlinear 3D pattern and have a different renewal rate. This work had two aims. First, to investigate whether the unusual distribution of cell populations reflects a similar distribution of functional activities. To this end, we determined the protein expression pattern of three well defined enterocytes functional markers: Peptide Transporter 1 (PepT1), Sodium-Glucose/Galactose Transporter 1 (SGLT-1) and fatty acid-binding protein 2 (Fabp2). Second, to characterize the structure of RT intestinal stem cells (ISC) niche and to determine whether the different proliferative rates correlate with a different organization and/or extension of the stem cells population. We studied the expression and localization of well-characterized mammal ISC markers: LGR5, HOPX, SOX9, NOTCH1, DLL1 and WNT3A. Our results indicate that morphological similarity is associated with similar function only between the first portion of the mid-intestine and the apical part of the complex folds in the second portion. Mammal ISC markers are all expressed in RT but their localization is completely different suggesting also substantial functional differences. Finally, higher renewal rates are supported by a more abundant ISC population.

Mast cells are tissue-resident immune cells distributed in all tissues and strategically located close to blood and lymphatic vessels and nerves. Thanks to the expression of a wide array of receptors, mast cells act as tissue sentinels, able to detect the presence of bacteria and parasites and to respond to different environmental stimuli. Mast cells originate from bone marrow progenitors that enter the circulation and mature in peripheral organs under the influence of microenvironment factors, thus differentiating in heterogeneous tissue-specific subsets. Even though mast cell activation has been traditionally linked to IgE-mediated allergic reactions, a role for these cells in other pathological conditions including tumor progression has recently emerged. However, several aspects of mast cell biology remain to be clarified. The advent of single-cell RNA sequencing platforms has provided the opportunity to understand mast cell origin and differentiation as well as the phenotype and functions within different tissues, including the gut. This review recapitulates how single cell transcriptomic studies provided insight into mast cell development as well as into the functional role of intestinal MC subsets in health and disease.

Abstract：To investigate the effects of feeding the Lincomycin and faecal bacterial on weaning stress in Tibetan piglets, we divided the weaned Tibetan piglets at 30 days of age into four groups. We measured growth performance, blood physiological indexes, and metabolomics. The results showed that the Ant, Tib, and Fec groups significantly reduced the ratio of diarrhoea to feed/weight (F/G) and increased the average daily gain (ADG) compared to the Nor group (p < 0.01). The Nor group had significantly lower leukocyte counts, hemoglobin levels, and erythrocyte counts compared to the other three groups on 21d (p < 0.05). These physiological indexes tended to stabilize on 42d. We found that there were beneficial metabolites and metabolic pathways for gastrointestinal function. Specifically, the porphyrin metabolic pathway was elevated in the Ant group, and the tryptophan metabolic pathway was significantly elevated in the Tib and Fec groups compared to the Nor group (p < 0.05). In conclusion, adding faecal bacterial supernatant and fifteen-flavour black pills of Tibetan medicine to the feed reduced the rate of diarrhoea and improved the growth performance of piglets. Moreover, it had an effect on microorganisms and their metabolites and pathways in the gastrointestinal tract of the animals, which might be the main reason for influencing the diarrhoea rate of weaned Tibetan piglets and the growth and development of the piglets. This study provides a new approach for anti-stress applications in weaned Tibetan piglets and the development of substitute anti-products.

Several chronic diseases derive from metabolic, genetic, or inflammatory causes and often these causes are interconnected. Pharmacological treatments, although effective, often lead to unpleasant side effects. In this context, preventive approaches are of growing interest. The literature data of recent years support that the dietary intake of bioactive compounds can positively influence the biological functions of an organism. Among the bioactive compounds in the diet, polyphenols are widely recognized for their beneficial effects on health, as useful compounds for preventing/combating a series of pathologies related to lifestyle, metabolism, and aging. The artichoke (Cynara scolymus L.), a member of the Asteraceae family, is widely used in the food and herbal medicine fields for its beneficial properties. Artichokes are rich in polyphenols (including cynarin), flavonoids and their derivatives, and, for this reason, they have aroused interest in their pharmacological properties. The best-known activity of polyphenols is antioxidant activity. Through it, they help to neutralize free radicals, preventing cellular damage and the subsequent risk of conditions such as cancer, diabetes, and heart disease. Related to the antioxidant action we find the anti-inflammatory activity. This is an important benefit since chronic inflammation is a cause or contributory cause of many chronic diseases. Although many scientific results are of great interest and potential, there are still gaps to be filled. In this review, we report and discuss new insights providing documented evidence regarding the benefits of the artichoke compounds and their possible use to support the pharmacological treatment of pathologies associated with inflammation.

Growing evidence suggests a possible involvement of the intestinal microbiota in generating new neurons, but a detailed breakdown of the microbiota composition is lacking. In this report, we systematically reviewed preclinical rodent reports addressing the connection between the composition of the intestinal microbiota and neurogenesis and neurogenesis-affecting neurotrophins in the hippocampus. Various changes in bacterial composition from low taxonomic resolution at the phylum level to high taxonomic resolution at the species level were identified. As for neurogenesis, studies predominantly used doublecortin (DCX) as a marker of newly formed neurons or bromodeoxyuridine (BrdU) as a marker of proliferation. Brain-derived neurotrophic factor (BDNF) was the only neurotrophin found researched in relation to the intestinal microbiota. Phylum Actinobacteria, genus Bifidobacterium and genus Lactobacillus found the strongest positive while phylum Firmicutes, phylum Bacteroidetes and family Enterobacteriaceae as well as germ-free status, showed the strongest negative correlation towards neurogenesis or BDNF mRNA expression. Age, short-chain fatty acids (SCFA), obesity and chronic stress were recurring topics in all studies identified. Overall, these findings add to the existing evidence of a connection between microbiota and processes in the brain. To better understand this interaction, further investigation based on analyses of higher taxonomic resolution and clinical studies would be a gain to the matter.

Iron and zinc are essential micronutrients required for growth and health. Deficiencies of these nutrients are highly prevalent among populations, but can be alleviated by supplementation. Cross-sectional studies in humans showed positive association of serum zinc levels with hemoglobin and markers of iron status. Dietary restriction of zinc or intestinal specific conditional knock out of ZIP4 (SLC39A4), an intestinal zinc transporter, in experimental animals demonstrated iron deficiency anemia and tissue iron accumulation. Similarly increased iron accumulation has been observed in cultured cells exposed to zinc deficient media. These results together suggest a potential role of zinc in modulating whole body iron metabolism. Studies in intestinal cell culture models demonstrate that zinc induces iron uptake and transcellular transport via induction of divalent metal iron transporter-1 (DMT1) and ferroportin (FPN) expression, respectively. It is interesting to note that intestinal cells are exposed to very high levels of zinc through pancreatic secretions, which is a major route of zinc excretion from the body. Therefore, zinc appears to be modulating the iron metabolism possibly via regulating the DMT1 and FPN1 levels. Herein we critically reviewed the available evidence to hypothesize novel mechanism of Zinc-DMT1/FPN axis in regulating intestinal iron absorption and tissue iron accumulation to facilitate future research aimed at understanding the yet elusive mechanisms of iron and zinc interactions.

Maintenance of intestinal barrier integrity is crucial for preventing inflammatory bowel diseases (IBDs) onset and exacerbations. In this work we study the effect of a fixed combination of Lactobacillus reuteri and Lactobacillus acidophilus and herbal extracts in an in vitro inflammation experimental model. Caco-2 cell monolayer was exposed to INF-γ+TNF-α or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin tight junctions (TJs) were also investigated by mean of immunofluorescence. The pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. In summary the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBDs conditions.

Abstract: Autism spectrum disorders (ASDs) are complex, lifelong, neurodevelopmental conditions of largely unknown cause. The global prevalence of autism has increased twentyfold to thirtyfold since the earliest epidemiologic studies were conducted in the late 1960s and early 1970s. Recent reports agree on the association of ASD with the alteration of the microbiome (dysbiosis), which raises the possible role of external factors. Our study aimed at identifying antibiotic classes that might be associated with the development of ASD-related dysbiosis either promoting or inhibiting the process. Statistical comparison was made between the average yearly consumption of different antibiotic classes (1997-2020) and the number of individuals living with ASD estimated for 2023/100000 population in 30 European countries and the results were statistically analyzed. Tetracycline (J01A) showed significant positive (promoting) association with the prevalence of ASD (Pearson r: 0.373, p: 0.043. OR: 1.312, CI95%: 0.995-1.791, p: 0.065) and narrow-spectrum, beta-lactamase resistant penicillin (J01CF) (Pearson r: 0.524, p: 0.003, OR: 3.240, CI95%: 1.710-8.853, p: 0.004, Kruskal-Wallis p: 0.032). Mild, negative (inhibitory) association was observed with broad-spectrum, beta-lactamase sensitive penicillin (J01CA) (Pearson r: -0.278, p: 0.157, OR: 0.808, CI95%: 0649-0957, p: 0.028) and narrow-spectrum, beta-lactamase-sensitive penicillin (J01CE) (Pearson p: -0.032, r: 0.865, OR: 0.725, CI95%: 0.543-0.885, p: 0,009). Our findings strongly support the animal experiments when penicillin-exposed newborn mice developed "autism-like" behavior.

Gut dysbiosis, alongside with high-fat diet and cigarette smoking, is considered one of the factors promoting coronary arterial disease (CAD) development. The present study aimed to research whether gut dysbiosis can increase bacterial metabolites concentration in the blood of CAD patients and what impact these metabolites can exert on endothelial cells. The gut microbiome of 15 CAD patients and age-matched 15 healthy controls was analyzed by metagenome sequencing. The in vitro impact of LPS and indoxyl sulfate at concentrations present in patients sera on endothelial cells was investigated. A metagenome sequencing analysis revealed gut dysbiosis in CAD patients, further confirmed by elevated levels of LPS and indoxyl sulfate in patients sera. CAD was associated with depletion of Bacteroidetes and Alistipes. LPS and indoxyl sulfate in meager concentrations demonstrated co-toxicity to endothelial cells inducing reactive oxygen species, E-selectin, and monocyte chemoattractant protein-1 (MCP-1) production and promoting thrombogenicity of endothelial cells confirmed by monocyte adherence. The co-toxicity of LPS and indoxyl sulfate was associated with harmful effects on endothelial cells, strongly suggesting that gut dysbiosis-associated increased intestinal permeability can initiate or promote endothelial inflammation and atherosclerosis progression.

Diet plays a pivotal role in the overall health of an individual. Not only does it help carry out and regulate certain physiological functions, but it also can determine the composition of the gut microbiome. While the relative number of microorganisms that make up the gut microbiome vary between individuals and can be dependent on different environmental factors, there is evidence to suggest that composition of the microbiome can correlate with overall health or disease. When the GI microbiome is disturbed or suddenly changes it results in microbiome dysbiosis, a condition that correlates with the presence of certain diseases. Diseases linked to microbiome dysbiosis range from metabolic disorders, inflammatory bowel diseases to disorders of the brain. Many of these diseases are linked to the connection between the brain and the gut, known as the brain-gut axis. This bidirectional communication is important to maintain normal intestinal function, but is also responsible for the GI response to emotions as well as the emotional response to GI disturbances. By exploiting the interaction between microbiome health and nutrition, diet can be used to alleviate disease symptoms, protect against the development of certain conditions, and better maintain overall health. This review will examine the effects of nutrition on the microbiome, diseases linked to disruption of the normal microbiome, and the way that altering the diet can mitigate symptoms or prevent disease.

Intestinal epithelial cell activities during homeostasis and regeneration are well described, but their potential interactions with stromal cells remain unresolved. Exploring the functions of these heterogeneous intestinal mesenchymal stromal cells (iMSCs) remains challenging due to the lack of specific markers for most functionally homogenous subpopulations. In recent years, however, novel clustering techniques such as single-cell RNA sequencing (scRNA-seq), fluorescence-activated cell sorting (FACS), confocal microscope, and computational remodeling of intestinal anatomy have helped identify and characterize some specific iMSC subsets. These methods help researchers learn more about the localization and functions of iMSC populations during intestinal morphogenic and homeostatic conditions. Furthermore, it is imperative to understand their cellular pathways for activation and how they interact with surrounding cellular components, particularly during intestinal epithelial regeneration that follows mucosal injury. This review provides insights into the spatial distribution and functions of some identified iMSC subtypes in intestinal morphogenesis, homeostasis, and regeneration. We reviewed related signaling mechanisms implicated during epithelial and subepithelial stromal cell crosstalk. Future research should focus on elucidating the molecular intermediates of these regulatory pathways to open a new frontier for potential therapeutic targets that can alleviate intestinal mucosa-related injuries.

The human gastrointestinal tract is inhabited by trillions of commensal bacteria collectively known as the gut microbiota. Our recognition of the significance of the complex interaction between the microbiota, and its host has grown dramatically over the past years. A balanced microbial community is a key regulator of the immune response, and metabolism of dietary components, which in turn, modulates several brain processes impacting mood and behavior. Consequently, it is likely that disruptions within the composition of the microbiota would remotely affect the mental state of the host. Here, we discuss how intestinal bacteria and their metabolites can orchestrate gut-associated neuroimmune mechanisms that influence mood and behavior leading to depression. In particular, we focus on microbiota-triggered gut inflammation and its implications in shifting the tryptophan metabolism towards kynurenine biosynthesis while disrupting the serotonergic signaling. We further investigate the gaps to be bridged in this exciting field of research in order to clarify our understanding of the multifaceted crosstalk in the microbiota-gut-brain interphase, bringing about a novel microbiota-targeted therapeutics for mental illnesses.

Acute peritonitis is a severe complication of abdominal surgery with a high mortality rate. Intes-tinal insufficiency syndrome (IIS) is a key factor in the progression of peritonitis, contributing significantly to morbidity and mortality. The most characteristic and rapid manifestation of IIS is the development of intestinal paresis. Intestinal paresis is a condition characterized by inhibi-tion of intestinal motility, with the inability to evacuate intestinal contents. Intestinal paresis is caused by a cascade of neuroreflex and humoral reactions that lead to severe microcirculatory and metabolic disturbances. In the absence of adequate treatment, IIS can progress to enteritis, a state of complete intestinal insufficiency, with the inability to absorb nutrients and water.

Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders, including coeliac disease (CD) and Crohn’s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear β-catenin expression, as well as in prognosis. For these patients, high tumor-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear β-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous β-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC.

Inflammatory bowel disease (IBD) is an incurable, chronic disorder of the gastrointestinal tract, whose incidence increases every year. Scientific research is constantly delivering new information about the disease and its multivariate, complex etiology. Nevertheless, full discovery and understanding of the complete mechanism of IBD pathogenesis still pose a significant challenge to today's science. Recent studies unanimously confirmed the association of gut microbial dysbiosis with IBD, as well as its contribution to the regulation of the inflammatory process. It transpires that not only the altered composition of pathogenic and commensal bacteria is characteristic of disturbed intestinal homeostasis in IBD, but also of viruses, parasites, and fungi, which are active in the intestine. In fact, the crucial function of microbial metabolome in the human body is altered, which causes a wide range of effects in the host, thus providing a basis for the disease. On the other hand, human genomic and functional research revealed more loci that play an essential role in gut homeostasis regulation, immune response, and intestinal epithelial function. This review aims to organize and summarize currently available knowledge concerning the role and interaction of crucial factors associated with IBD pathogenesis, particularly host genetic composition, intestinal microbiota, and metabolome, with immune regulation.

Gut luminal dysbiosis and pathobiosis result in compositional and biodiversify alterations in the microbial and host co-metabolites. The main mechanism of bacterial evolution is horizontal gene transfer (HGT) and acquisition of new traits can be achieved through mobile genetic element (MGEs) exchange. Introducing genetically engineered microbes (GEMs) might break the harmonized balance in the intestinal compartment. The present objectives are: 1. To reveal the role played by GEMs' horizontal gene transfers in changing the landscape of the enteric microbiome eubiosis 2. To expand on the potential detrimental effects of those changes on human genome and health. A search of articles published in PubMed/MEDLINE, EMBASE, and Scielo from 2000 to august 2023, using appropriate MeSH entry terms were performed. GEMs' horizontal gene exchanges might induce multiple human diseases. The new GEMs can change the long-term natural evolution of the enteric pro- or eukaryotic cells inhabitants. The worldwide regulatory authority's safety control of GEMs is not enough to protect public health. Viability and biocontainment and many other aspects are only partially controlled and harmful consequences for public health should be avoided. Always remember that prevention is the most cost- effective strategy and "primum non nocere" is the name of the game.

In 2001, the first author of this paper reported that schizophrenia is associated with an increased frequency of the haptoglobin (Hp)-2 gene. The precursor of Hp-2 is zonulin, a molecule that affects intercellular tight junction integrity. Recently, we reported increased plasma IgA/IgM responses to Gram-negative bacteria in deficit schizophrenia indicating leaky gut and gut dysbiosis. The current study was performed to examine the integrity of the paracellular (tight and adherens junctions) and transcellular (cytoskeletal proteins) pathways in deficit versus non-deficit schizophrenia. We measured IgM responses to zonulin, occludin, E-cadherin, talin, actin and vinculin in association with IgA responses to Gram-negative bacteria, CCL-11, IgA responses to tryptophan catabolites (TRYCATs), immune activation and IgM to malondialdehyde (MDA) and NO-cysteinyl in 78 schizophrenia patients and 40 controls. We found that the ratio of IgM to zonulin + occudin / talin + actin + viculin (PARA/TRANS) was significantly greater in deficit than in non-deficit schizophrenia and higher in schizophrenia than controls and was significantly associated with increased IgA responses to Gram-negative bacteria. IgM responses to zonulin were positively associated with schizophrenia (versus controls), while IgM to occludin was significantly associated with deficit schizophrenia (versus non-deficit schizophrenia and controls). A large part of the variance (90.8%) in negative and PHEM (psychosis, hostility, excitation and mannerism) symptoms was explained by PARA/TRANS ratio, IgA to Gram-negative bacteria, IgM to E-cadherin and malondialdehyde (MDA) and memory dysfunctions, while 53.3% of the variance in the latter was explained by PARA/TRANS ratio, IgA to Gram-negative bacteria, CCL-11, TRYCATs and immune activation. The results show an upregulated paracellular pathway with breakdown of the tight and ahherens junctions and increased bacterial translocation in deficit schizophrenia. These dysfunctions in the intestinal paracellular route together with lowered natural IgM, immune activation and production of CCL-11 and TRYCATs contribute to the phenomenology of deficit schizophrenia.

Autism Spectrum Disorder (ASD) is characterized by varying degrees of difficulty in social interaction and communication. These deficits are often associated with gastrointestinal symptoms, indicating alterations in both intestinal microbiota composition and metabolic activities. The intestinal microbiota influences the function and development of the nervous system. In individuals with ASD, there is an increase in bacterial genera such as Clostridium, as well as species involved in the synthesis of branched-chain amino acids (BCAA) like Prevotella copri. Conversely, decreased amounts of Akkermansia muciniphila, and Bifidobacterium spp. are observed. Epigallocatechin gallate (EGCG) is one of the polyphenols with the greatest beneficial activity on microbial growth and its consumption is associated with reduced psychological distress. Therefore, the objective of this review is to analyze how EGCG and its metabolites can improve the microbial dysbiosis present in ASD and its impact on the pathology. The analysis reveals that EGCG inhibits the growth of pathogenic bacteria like Clostridium perfringens and Clostridium difficile. Moreover, it increases the abundance of Bifidobacterium spp. and Akkermansia spp. As a result, EGCG demonstrates efficacy in increasing the production of metabolites involved in maintaining epithelial integrity and improving brain function. This identifies EGCG as highly promising for complementary treatment in ASD.

Background and objectives: Alzheimer's disease (AD) is a progressive neurodegenerative illness, responsible for 60-70% of all dementias, affecting over 50 million people worldwide, and nearly 11 million in European countries. Several putative factors are identified in the literature as causative agents or risk factors for the development of AD. The amyloid cascade hypothesis has been the main hypothesis about the pathophysiology of AD for decades. Recent studies raised the possible role of dysbiosis in the development of AD which prevents memory loss. The amyloid-β (Aβ) deposition might be considered as an inflammatory reaction to certain molecular products arising from the altered microbiome. Based on the above observations, it has been suspected, that antibiotic consumption patterns of different antibiotic classes might be associated with the prevalence of AD in European countries. Methods: Antibiotic consumption (ECDC) for 1997-2007, 2008-2018, and as the whole 1997-2018 period, have been compared to the AD prevalence for 2018 expressed in percentage of the population and statistically analyzed by Pearson calculation. Results: A significant positive correlation has been found between the AD prevalence (2018) and the average quinolone consumption for the year 1997-2007 (p: 0.044). A similar association was not observed for the entire 22 years (1997-2018) of the average quinolone consumption, and the years 2008-18, indicating 10-20 years of time-lapse between the antibiotic exposure and the development of AD. The ratio of broad-spectrum and narrow-spectrum antibiotics (B/N) estimated in the ECDC database for the years of 2008-2018 showed a strong positive association with AD prevalence (2018) (p: 0.026) and a positive correlation tendency for the entire 22 years 1997-2018 (p: 0.063), but none for the years 1997-2007 (p: 0.241). Broad-spectrum, beta-lactamase sensitive penicillin (J01CA) consumption showed a positive (non-significant) correlation with the prevalence of AD for the years 2008-2018 (p:0.080).Discussion: Our study indicated the possible sequential role of certain classes of antibiotics in the development of dysbiosis leading to amyloid deposits of AD, which strengthen the possible role of different mediator molecules (short-chain fatty acids, lipopolysaccharides, etc.) produced by the altered microbiome in the development of AD.

Intestinal microbiota attracts daily attention of a growing number of study which have attempted to link gut dysbiosIs with a variety of disease states: irritable bowel syndrome (IBS), inflamed bowel disease (IBD), Crohn's disease (CD), leaky gut syndrome (LGS), food intolerance, diabetes, metabolic syndrome, cancer, etc.. In our study we analyzed how intestinal dysbiosis may be related to chronic fatigue syndrome (CFS) and depression through the exchange of information through the gut-brain axis (GBA). We studied 33 subjects, 13 males and 20 females, who reported CFS or/and depression: we investigated their salivary cortisol levels, blood serotonin, omega 3/6 ratio, intestinal dysbiosis (calculated on the urinary levels of indoxyl sulfate and skatole), and we looked for the presence of Candida a. or mycetes in the stool; the data accumulated with this research show a correlation between the presence of Candida a./miceti, indoxyl sulfate urine values beyond the physiological and low serotonin levels. In addition, data analysis showed that the EPA/DHA values also show pro-inflammatory levels in case of dysbiosis and low serotonina levels. The relationship, however, with cortisol levels requires further research although this study showed a statistically significant positive correlation between these values, measured at specific times, and serotonin levels. Aims its connections with We investigated the relationship between stress (evaluated through the measurement of salivary cortisol levels) and gastrointestinal efficiency measured as a function of intestinal fermentative and putrefactive dysbiosis, evaluating the levels of urinary indoxyl sulfate in the first case (a possible correlation with the presence of Candida spp or Mycetes in the subjects feces was investigated), urinary skatole levels in the second one, in patients with chronic fatigue syndrome (SFC) and depression. In these patients we also have studied omega 3/6 ratio, and finally we have analized the impact that the alteration of these parameters can have on the serotonin levels. This research attemps to highlight the contact points, in some cases not so obvious, among these topics, contact points that, although they give us interesting indications, show the need to be further deepened by analyzing a larger amount of data.

Understanding the spatially varying effects of demographic factors on the spatio-temporal variation of intestinal parasites infections is important for public health intervention and monitoring. This paper presents a hierarchical Bayesian spatially varying coefficient model to evaluate the effects demographic factors on intestinal parasites morbidities in Ghana. The modeling relied on morbidity data collected by the District Health Information Management Systems. We developed Poisson and Poisson-gamma spatially varying coefficient Models. We used the demographic factors, unsafe drinking water, unsafe toilet and unsafe liquid waste disposal as model covariates. The models were fitted using the Integrated Nested Laplace Approximations (INLA). The overall risk of intestinal parasites infection was estimated to be 10.9 per 100 people with a wide spatial variation in the district-specific posterior risk estimates. Substantial spatial variation of increasing multiplicative effects of unsafe drinking water, unsafe toilet and unsafe liquid waste disposal occurs on the variation of intestinal parasites risk. The structured residual spatial variation widely dominates the unstructured component, suggesting that the unaccounted-for risk factors are spatially continuous in nature. The study concludes that both the spatial distribution of the posterior risk and the associated exceedance probability maps are essential for monitoring and control of intestinal parasites.

The present study examined metabolites in Northern wild rice (WLD), the impact of WLD supplemented high fat (HF) diet on gut microbiota, short chain fatty acids (SCFAs) and correlation with metabolism or inflammation versus HF+white rice (WHR) in mice. C57BL/6J mice received HF diet supplemented with 26g% WHR, 26g% WLD, or 13g% WHR+13g% WLD (WTWD) for 12 weeks. The levels of fasting plasma glucose, total cholesterol, triglycerides, insulin resistance, inflammatory cytokines and monocyte adhesion were lower, and the abundances of fecal Lactobacillus gasseri species bacteria and propionic acid were higher in HF+WLD diet-fed mice compared to HF+WHR diet-fed mice (p<0.05). The anti-inflammatory effects of HF+WTWD diet were weaker than that in HF+WLD diet, but were greater than that in HF+WHR diet-fed mice (p<0.05). Relative abundances of fecal Lactobacillus gasseri and propionic acid in HF+WLD fed-mice were higher than that in HF+WHR fed mice. The abundance of fecal L. gasseri and propionic acid negatively correlated with metabolic and inflammatory markers (p<0.05). The findings suggest that WLD dose-dependently attenuated metabolic and inflammatory disorders in HF diet-fed mice. Interactions between WLD components and gut microbiota may upregulate fecal propionic acid and contribute to metabolic and anti-inflammatory benefits of WLD diet-induced insulin resistant mice.

The combination of freeze-dried aronia, red ginseng, ultraviolet-irradiated shiitake mushroom and natokinase (AGM; 3.4: 4.1: 2.4: 0.1) was examined to evaluate its effects on insulin resistance, insulin secretion and gut microbiome in a non-obese type 2 diabetic animal model. Pancreatectomized (Px) rats were provided high fat diets supplemented with either of 1) 0.5 g AGM (AGM-L), 2) 1 g AGM (AGM-H), 3) 1 g dextrin (control), or 4) 1g dextrin with 120 mg metformin (positive-control) per kg body weight for 12 weeks. AGM (1 g) contained 6.22 mg cyanidin-3-galactose, 2.5 mg ginsenoside Rg3 and 0.6 mg β-glucan. Px rats had decreased bone mineral density in the lumbar spine and femur and lean body mass in the hip and leg compared to the normal-control and AGM-L and AGM-H prevented the decrease. Visceral fat mass was lower in the control group than the normal-control group and its decrease was smaller by AGM-L and AGM-H. HOMA-IR was lower in descending order of the control, positive-control, AGM-L, AGM-H and normal-control groups. Glucose tolerance was deteriorated in the control group and it was improved by AGM-L and AGM-H more than in the positive-control group. Glucose tolerance is associated with insulin resistance and insulin secretion. Insulin tolerance indicated insulin resistance was highly impaired in diabetic rats, but it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Insulin secretion capacity, measured by hyperglycemic clamp, was much lower in the control group than the normal-control group and it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Diabetes modulated the composition of gut microbiome and AMG prevented the modulation of gut microbiome. In conclusion, AGM improved glucose metabolism by potentiating insulin secretion and reducing insulin resistance in insulin deficient type 2 diabetic rats. The improvement of diabetic status alleviated body composition changes and prevented changes of gut microbiome composition.

This study was conducted with the objective of investigating the enrichment of weaned piglet diets with organic selenium (proteinate selenium) and inorganic selenium (sodium selenite) with two addition levels (0.15 and 0.30 mg/kg). A total of 40 piglets (20 castrated males and 20 females) weaned at 28 days of age with an average initial weight of 6.60±1.06 kg were used. The treatments were: Control diet (Control diet); Selenium-enriched control diet proteinate with 0.15 mg/kg of selenium added (SeOrg-0.15); Selenium-enriched control diet proteinate with 0.30 mg/kg of selenium added (SeOrg-0.30); Control diet enriched with sodium selenite with 0.15 mg/kg of selenium added (SeInorg-0.15); and Control diet enriched with sodium selenite with 0.30 mg/kg of selenium added (SeInorg-0.30). The presence of selenium in the control diet came from the ingredients and the mineral supplement. The following data were analyzed: productive performance; digestibility of nutrients and energy; morphometry and intestinal integrity; serum biochemical parameters; and gene expression of selenoproteins in intestinal epithelium and liver tissue of piglets. The SeOrg-0.30 treatment caused a reduction (P

Background: Globally, about 3.5 billion people are affected by intestinal parasitic infections (IPIs). This study aimed to investigate the effects of IPIs on intestinal wall thickness and its potential association with hypertension in different genders. Methods: A total of 108 subjects, including 83 consecutive patients with symptomatic and laboratory-confirmed IPIs (male = 48; female = 35) and 25 healthy controls (male = 10; female = 15), were recruited. B-mode ultrasound grayscale and color images of the duodenum and colon were obtained with and without water contrast. Results: Patients with IPIs had a tendency towards greater duodenal wall thickness (DUOTHICK = 0.88 ± 0.73 cm) compared to controls (0.595 ± 0.089 cm), p = 0.056. Patients with IPIs also had significantly greater ascending colon wall thickness (ASCTHICK = 1.076 ± 0.29 cm) and descending colon wall thickness (DSCTHICK = 1.175 ± 0.366 cm) compared to controls (ASCTHICK = 0.6015 ± 0.1607 cm, DSCTHICK = 0.6223 ± 0.135 cm), p < 0.05. Men over 50 years had greater DSCTHICK (1.25 ± 0.434 cm) than post-menopausal women (0.986 ± 0.389 cm), p < 0.05. DSCTHICK significantly predicted diastolic blood pressure (β = -0.295, p < .05) and blood sodium level (β = -0.300, p < .05). Conclusion: We demonstrated the effects of IPIs on the intestinal microbiome causing intestinal wall cytoskeletal dysfunction, which led to the development of a "leaky gut syndrome."

This study was aimed to investigate the effect of xylan depolymerizing enzyme namely endo-xylanase (Xyn) combined with debranching enzymes namely arabinofuranosidase (Afd) and feruloyl esterase (FE) on digestion, growth performance and intestinal volatile fatty acid profile of piglets. The in vitro experiments were firstly conducted to examine the enzymological properties of Xyn, Afd and FE, the synergy among these enzymes, together with the effect of combination of these enzymes on digestion of piglet diet. The in vivo experiment was then implemented by allocating 270 35-d-old postweaning piglets into 3 treatment groups: control group, Xyn group and (Xyn+Afd+FE) group. Each group had 6 replicates (15 piglets/replicate). The results revealed a satisfying thermostability and pH stability of Xyn, Afd and FE. Combination of Xyn, Afd and FE had a superiority (P < 0.05) over Xyn alone and its combination with Afd or FE in promoting degradation of different bran fibers rich in arabinoxylan (Abx). Treatment with combination of Xyn, Afd and FE had advantages over Xyn alone to induce increasing trends (P < 0.10) of in vitro digestibility of dietary nutrients (dry matter, crude protein, crude ash and gross energy) and piglet growth performance (average daily gain, final body weight and feed efficiency), concurrent with a reduction (P < 0.05) of diarrhea rate and increases (P < 0.05) in cecal acetic acid, butyric acid and total volatile fatty acids concentrations as well as pH value of piglets. Collectively, combination of Xyn, Afd and FE was efficient in benefiting degradation of Abx in brans, as well as improving digestion, growth performance and intestinal volatile fatty acid profile of piglets.

Fat reduction and anti-inflammation are commonly claimed properties of probiotics. Lactobacillus plantarum and Enterococcus faecium were tested in high fat-induced obesity mice and in vitro experiments. After 16 weeks of probiotics, L. plantarum outperforms E. faecium on the anti-obesity property as indicated by body weight, regional fat accumulation, serum cholesterol, inflammatory cytokines (in blood and colon tissue), and gut barrier defect (FITC-dextran assay). With fecal microbiome analysis, L. plantarum but not E. faecium reduced fecal abundance of pathogenic Proteobacteria without an alteration in total Gram-negative bacteria when compared with non-probiotics obese mice. With palmitic acid induction, the condition media from both probiotics similarly attenuated supernatant IL-8, improved enterocyte integrity and down-regulated cholesterol absorption-associated genes in Caco-2 cell (an enterocyte cell line) and reduced supernatant cytokines (TNF-α and IL-6) with normalization of cell energy status (extracellular flux analysis) in bone-marrow-derived macrophages. Because the anti-inflammatory effect of the condition media of both probiotics on palmitic acid-activated enterocytes was neutralized by amylase, the active anti-inflammatory molecules might, partly, be exopolysaccharides. As L. plantarum out-performed E. faecium in anti-obesity property, possibly through the reduced fecal Proteobacteria, with a similar anti-inflammatory exopolysaccharide; L. plantarum is a potentially better option for anti-obesity than E. faecium.

Trichinellosis is a major worldwide health concern caused by T. spiralis infection without highly efficient and safe therapeutic method so far. To solve the problem of uncomplete drug treatment schemes and the rise of anthelmintic resistance, a potential protective effect of probiotic strains against zoonotic T. spiralis infection was investigated in the framework of a new therapeutic strategy aimed at using probiotics to control parasitic zoonoses. The study was focused on L. reuteri protected against T. spiralis infection in intestinal phase throughout the detection of adult worm number, inflammatory factors mRNA expression, antioxidant enzyme expression and Nrf2 signal pathway protein expression. Mice were divided randomly into 3 groups: 1) Control group: no treatment; 2) Ts group: T. spiralis infection; 3）LAB group: T. spiralis infected after orally administered L. reuteri for 7 days. Probiotics bacteria were administered daily in a dose of 109 CFU/mL, and mice were infected with 400 T. spiralis larvae in the experimental groups. The number of adult worms was also significantly increased after administration of probiotics. Meanwhile, L. reuteri alleviate the inflammatory response caused by T. spiralis infection in intestinal has been confirmed. In addition, the promotion of antioxidant enzyme expression can be inferred that L. reuteri regulate Nrf2 signal pathways against T. spiralis infection. Our study demonstrates that L. reuteri provide protection against T. spiralis infection in intestinal. Therapeutic approaches with probiotic strains admission could help to reduce the risks of trichinellosis or complement classical anti-parasite treatments.

Exercise affects various organs. However, its effects on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training in-creases the expression of carbohydrate digestion and absorption molecules. Exercise was also shown to increase the concentration of blood glucagon like peptide-2(GLP-2), which regulates carbohydrate digestion and absorption in small intestinal epithelium. Therefore, we investigated the effects of exercise on intestinal digestion and absorption molecules and the levels of GLP-2. 6-wk-old of male mice were divided into 2 groups; sedentary (SED) and low-intensity exercise (LEx). LEx mice were required to run on a treadmill (12.5 m/min, 60 min), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest and plasma, jejunum, ileum, and colon were sampled. Samples were analyzed using EIA and immunoblotting. The levels of plasma GLP-2 and the expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter (GLUT2) in the jejunum were increased in LEx group. We showed that acute low-intensity exer-cise affects the intestinal carbohydrate digestion and absorption molecules via GLP-2. Our results suggest that exercise might provide new benefits to the small intestine for people with intestinal frailty.

Aim: This study aims to analyze the collaborative structure of Intestinal Behçet’s Disease (IBD) research by examining co-authorship networks in publications indexed in the Web of Science (WoS) Core Collection from 2000 to 2023. The goal is to identify key researchers, institutions, and collaboration patterns that have shaped the field over the past two decades. Method: This study utilized network analysis techniques to evaluate 484 publications related to IBD research indexed in the WoS Core Collection between 2000 and 2023. The analysis was conducted using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The co-authorship networks were assessed using macro-level indicators such as network density (the ratio of actual to possible connections), clustering coefficient (degree of node clustering), number of components (distinct connected subgroups), and average path length (average distance between nodes). Micro-level indicators including degree centrality (importance based on the number of connections), closeness centrality (proximity to other nodes), and betweenness centrality (frequency of a node on the shortest paths between others) were also analyzed.Result: From 2000 to 2009, the co-authorship network was highly fragmented with a low network density of 0.0114 and 84 distinct components, indicating limited collaboration. Key contributors during this period included Kim, Won Ho, and Cheon, Jae Hee (South Korea), who played central roles in connecting disparate research clusters. In the following decade (2010-2019), network density decreased slightly to 0.0086, and the number of components increased to 113, reflecting continued fragmentation despite growing research output. However, from 2020 to 2023, network density increased to 0.0171, and the number of components decreased to 73, indicating a trend towards greater integration and collaboration. Notable researchers in this period included Emmi, Giacomo (Italy), and Hatemi, Gulen (Turkey), who emerged as central figures, highlighting a shift in research leadership from Asia to Europe..Conclusion: The co-authorship network analysis of IBD research reveals an evolving collaborative landscape with increasing network density and decreasing fragmentation over time, particularly in the most recent period. From 2000 to 2019, Japanese and Korean researchers were prominent contributors, highlighting the significance of Asia in the global research arena. However, since 2020, researchers from Italy and Turkey have gained significant international prominence, suggesting a shift in the research focus from Asia to Europe. This transition may be attributed to changes in the incidence rates of IBD, where rapid increases were observed in Asian countries like Japan, Korea, and China until 2020, followed by stabilization or decline, while incidence rates have been increasing in European countries such as Italy and Turkey. These findings underscore the importance of expanding international collaborations to enhance the understanding of IBD. Fostering global partnerships could further advance the field, promoting more integrated and innovative research efforts, and addressing the shifting dynamics of IBD prevalence across regions.

Intestinal Parasitic infections are one of the most common infections in tropics. There is paucity of data on prevalence of intestinal parasite infections among migrant construction workers and their house holds so this study was taken up. A cross sectional study was conducted for eight months with an aim to determine the prevalence and assess the associated risk factors among the households of migrant construction workers at AIIMS Bhopal. A semi-structured interview questionnaire survey was conducted prior to collection of stool samples. Each stool sample was examined macroscopically followed by occult blood testing. Wet mount observation was followed by modified acid fast staining and formal ether sedimentation. Recruits with pathogenic parasites in any of the three samples were considered positive and treated as per the national guidelines for age, drug and dose by clinical consultation. 361 participants were recruited. 122/361 (33.8%) were between 21 to 30 years. 55.2% females, 47.4% had occupation of digging soil, 93.1% practiced open field defecation. 36.9% (133/361) was the prevalence of intestinal parasitic infection. 88.7% monoinfection, E.histolytica/dispar (41%) and H.nana( 10.2%) were most prevalent parasites. 26.7%) was commonest. 11.28%coinfection, G. intestinalis with A. duodenale (26.7%) was commonest. In our study only hand washing was independent predictor having Odds Ratio of 3.6 with confidence interval 1.00-13.00(those who don’t wash hands before meals are 3.6 times more likely to develop infection). Only few studies address migrant construction workers, their nomadic behaviour makes them vulnerable for intestinal parasitic infections and not benefitting from prevention programmes as deworming programme.

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein, Neuroligin-3, was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3R451C mice bred on a mixed genetic background. Here we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3R451C mice show faster gastrointestinal transit in vivo and have longer small intestines compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3R451C mice, we observed a decrease in resting jejunal diameter and neurally-regulated dysmotility as well as shorter durations of contractile complexes in the ileum. In Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent by the GABAA antagonist, gabazine, compared to wild-type mice. Inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum, but not the ileum, in both wild-type and Nlgn3R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.

This study aimed to investigate the interactions between corn particle size (PS) and conditioning temperature (CT) on the performance, carcass traits, intestinal morphology, and immune responses in broilers fed a corn-soybean meal-based diet. A total of 360, one-day-old male broiler chicks (Ross 308) were randomly allocated into six dietary treatments in a 2×3 factorial arrangement, consisting of two corn PS (finely ground with geometric mean diameter (GMD) of 357 µm (PSF) vs. coarsely ground corn with GMD of 737 µm (PSC), and three CT [unconditioned (CTU), conditioned at 75◦C (CT75) and 90◦C (CT90)]. Birds accommodated in 30 pens with five replicates and 12 chicks per each. There was no interaction between corn PS and CT on growth performance and immune response of broilers at any growth phases. However, during the starter (0-10d) period, the average daily weight gain (ADWG) and feed conversion ratio (FCR) of PSF-fed birds were significantly improved compared to those fed PSC (P<0.05). During the starter (0-10d) and grower (11-24d) periods, increasing the conditioning temperature of corn increased the ADWG, while in the starter phase only the CT75 caused a lower FCR (P<0.05). Broilers fed PSF corn showed lowest FCR during the finisher (25-42d) period compared to those fed PSC (P<0.05). Conditioning corn at 75ºC reduced FCR during the finisher (25-42d) period compared to the birds fed CTU and CT90 corn (P<0.05). In whole experimental periods (1-42d), PSF and CT75 treatment increased the ADWG compared to the PSC and CTU (P<0.05). The CT75 treatment improved primary total anti-sheep red blood cell (SRBCs) titer (IgT) and IgM and secondary IgT and IgG responses compared to the other experimental groups (CTU and CT90) (P<0.05). No significant PS × CT interaction was found on Newcastle disease (ND) antibody titer of broiler chickens (P>0.05). Feeding CT75 corn reduced duodenum and jejunum relative length compared to the birds fed diets containing CTU corn. Significant PS×CT interactions (P<0.05) were observed for villus height, villus height to crypt depth, crypt depth, muscle thickness, and absorption surface area of jejunum. The highest carcass yield observed in PSF-CT75-group (P<0.05). In conclusion, the use of finely ground corn (PSF) conditioned at 75℃ (CT75) was beneficial to growth performance, development of the digestive tract, jejunum histomorphometry and the immune responses of broilers.

Submucosal invasion is a critical step in gastric cancer (GC) progression, which greatly enhances metastasis risk. Cancer stem cells are responsible for invasion, metastasis, and tumor growth. To identify stem cell-related markers associated with submucosal invasion in GCs, we investigated the expression of candidate cancer stem cell (CSC) markers (CD133, CD44, and ALDH1A) and intestinal stem cell (ISC) markers (EPHB2, OLFM4, and LGR5) in early GCs with submucosal invasion. Remarkably, expression of all ISC markers and CD133 was frequently confined to the basal area of the lamina propria (basal pattern) in mucosal cancer. The proportion of stem cell marker-positive cells substantially increased during submucosal invasion. Given that ISC markers are restricted to the crypt base of the normal intestinal mucosa, these findings suggest that many early GCs may retain hierarchical characteristics. CD44 expression showed a focal pattern, ALDH1A was predominantly expressed diffusely, and there was no expansion of CD44 or ALDH1A expression in the submucosal cancer cells. RSPO2 from muscularis mucosa seem to be partly responsible for the increased expression of ISC markers in GC cells at the basal areas. We also found that ISC markers were correlated with CDX2 expression in GCs, indicating that ISC markers are involved in the intestinal differentiation in GCs. Interestingly, ISC markers (EPHB2 and OLFM4) and CD133 showed a positive impact on clinical outcomes. In particular, the prognostic value of EPHB2 was significant for intestinal-type GCs in a multivariate analysis. In summary, ISC markers and CD133 showed a basal distribution pattern along with enhanced expression in submucosal invading cells in early GCs. EPHB2 was an independent prognostic marker in intestinal-type GCs.

Background: Obesity and Type 2 diabetes (T2D) promote inflammation, increasing the risk of colorectal cancer (CRC). High-fat diet (HFD)-induced obesity plays a key role in these diseases through biological mechanisms. This study examined the effect of genetic background on the multimorbidity of intestinal cancer, T2D, and inflammation due to HFD-induced obesity. Methods: A cohort of 357 Collaborative Cross (CC) mice from 15 lines was fed either a control chow diet (CHD) or HFD for 12 weeks. Body weight was tracked biweekly, and blood glucose was assessed at weeks 6 and 12 via intraperitoneal glucose tolerance tests (IPGTT). At the study's endpoint, intestinal polyps were counted, and cytokine profiles were analyzed to evaluate the inflammatory response. Results: HFD significantly increased blood glucose levels and body weight, with males showing higher susceptibility to T2D and obesity. Genetic variation across CC lines influenced glucose metabolism, body weight, and polyp development. Mice on HFD developed more intestinal polyps, with males showing higher counts than females. Cytokine analysis revealed diet-induced variations in pro-inflammatory markers like IL-6, IL-17A, and TNF-α, differing by genetic background and sex. Conclusions: Host genetics plays a crucial role in susceptibility to HFD-induced obesity, T2D, CRC, and inflammation. Genetic differences across CC lines contributed to variability in disease outcomes, providing insight into the genetic underpinnings of multimorbidity. This study supports gene-mapping efforts to develop personalized prevention and treatment strategies for these diseases.