Clostridioides difficile is a Gram-positive pathogen known for its toxin production and spore formation. It is primarily responsible for most cases of antibiotic-associated diarrhea. Bacterial persisters are a small subset of the population that exhibits transient tolerance to bactericidal substances, and they are of significant medical concern due to their association with the emergence of antibiotic resistance and difficult-to-treat chronic or recurrent infections. Vancomycin, the predominant antibiotic utilized in the management of C. difficile infection, is extensively applied in the realm of clinical practice. Previous studies have demonstrated a persister-like phenotype with treatments involving this antibiotic. However, the mechanism in C. difficile remains largely unknown, primarily due to the challenge of isolating this small population at any given time. To better characterize C. difficile persister cells, we present a study that enables the enrichment and characterization of persister cells from bacterial cultures in both exponential and stationary phases. Moreover, we could differentiate between triggered (induced by antibiotics, such as vancomycin) and spontaneous (stochastic) persister cells. Additionally, we observed the involvement of toxin-antitoxin systems and Clp proteases in persister cell formation.

The gut microbiota's part in colon cancer has become an exciting and hopeful area of study because it shows complex links that affect how cancer starts, spreads, and responds to treatments. Dysbiosis, which is an imbalance in the community of germs in the gut, has been linked to a higher risk of colon cancer by causing inflammation and making a place where tumours can grow. Researchers have found that some kinds of bugs can either help colon cancer grow or stop it from doing so. This shows how important it is to maintain a healthy gut bacteria. In both preclinical and clinical research, therapeutic treatments that target the microbiome in the gut have shown promise. Probiotics and prebiotics can change the environment around a tumour, change the balance of microorganisms in the gut, and boost immune responses that fight the cancer. Faecal microbiota transfer (FMT) is being looked at as a new way to change the bacteria in the guts of people with colon cancer. By adding microbiota-targeted drugs to standard cancer treatments, it may be possible to make the treatment more effective and lessen side effects. Microbiota-focused treatments for colon cancer are still in their early stages, but they show promise. More research needs to be done to find out how they work and show that they work in the clinic. The link between the bacteria in the gut and colon cancer opens up new ways to help patients and give them better results. This might make a difference in how colon cancer is handled in the future.

Colorectal cancer is third most common malignancy. For metastasis of rectal cancer, metastasis to skeletal muscle tissue is rare. In this case report, we describe a 51-year-old male patient with rectal cancer with neoadjuvant concurrent radiotherapy and chemotherapy followed by transanal total mesorectal excision with ileostomy. However, he had deep venous thrombosis of left leg after operation and skeletal muscle metastasis was diagnosed via tissue proof. Therefore, less possibility of metastasis increased included brain, duodenum, bone, and nervous system. The prognosis of metastasis to skeletal muscle is poor in contrast to liver or lung metastasis.

Microbiota and the metabolites they produce within the large intestine interact with the host epithelia under the influence of a range of host-derived metabolic, immune, and homeostatic factors. This complex host-microbe interaction affects intestinal tumorigenesis but established microbial or metabolite profiles predicting colorectal cancer (CRC) risk are missing. Here we describe alterations in fecal bacteria and volatile organic compounds (VOC) in healthy (Non-Adenoma, NA) versus CRC prone (High-Risk Adenoma, HRA) individuals. Analyzing samples from 117 participants undergoing routine colonoscopy we highlight the higher abundance of Proteobacteria and Parabacteroides distasonis, and the lower abundance of Lachnospiraceae species, Roseburia faecis, Blautia luti, Fusicatenibacter saccharovorans, Eubacterium rectale and Phascolarctobacterium faecium, in the fecal samples of HRA individuals. Volatolomic analysis reveals higher concentration in the feces of HRA individuals of 5 compounds, isobutyric acid, methyl butyrate, methyl propionate, 2-hexanone and 2-pentanone. Interestingly, there is a level of complexity revealed by assessing fecal bacteria-VOC associations and another one by assessing differences in these associations between NA and HRA individuals. For example, isobutyric acid corelates positively with the Lachnospiraceae incertae sedis and Bacteroides genera in NA individuals, and negatively in HRA individuals. In contrast, Coprococcus and Colinsella genera correlate negatively with isobutyric acid in NA individuals, and positively in HRA individuals. The described differences in the fecal microbiota and VOC profiles and their associations in NA versus HRA individuals indicate the significance of multiple levels of combinatorial analysis towards the identification of testable CRC risk biomarkers.

Indocyanine Green (ICG) has significantly advanced minimally invasive surgery. It is widely recognized for its ability to visualize blood vessel patency in real-time across various surgical specialties. While its primary use in colorectal surgery is to evaluate anastomoses for leaks, nu-merous other applications have been documented in the literature. In this review, we aim to explore both established and emerging applications of ICG fluorescence in colorectal surgery, with the goal of improving patient outcomes. This includes preoperative tumor marking and the detection of metastatic disease. Some applications, such as lymphatic mapping, require further research to determine their impact on clinical practices. Conversely, oth-ers, like the intraoperative localizations of ureters, necessitate additional procedures and are not yet widely accepted by the surgical community. However, the development of alternative com-pounds could offer better solutions. Future research should focus on areas like quantitative ICG and protocol standardization in prospective multicenter studies.

It has been demonstrated that cancer cells that have survived cancer treatment may be more malignant than the original cancer cells. These cells are considered to be the main cause of metastasis in prognosis. A Nanog-overexpressing colon-26 (Nanog+colon26) was generated and its metastatic potential was confirmed to be enhanced, indicating higher malignancy. Extracellular vesicles (EVs) secreted from the cell line (Nanog+colon26EVs) were administered to mice at 5 μg nine times (three times per week for three weeks) via the tail vein (PBS was used as a control). Subsequently, Nanog+colon26 cells were administered to mice via the spleen, and the quantity of metastatic colonies in the liver was analyzed two weeks later. The results demonstrated that the administration of EVs suppressed metastasis. The enhanced phagocytic activity of macrophages observed in the group treated with Nanog+colon26EVs indicated the involvement of the immune system in the observed metastasis-suppressing effect. Small RNA sequencing was conducted to identify Nanog-dependent miRNAs that exhibited significant changes (Fc>=1.5 or Fc

This study focuses on the potential medicinal properties of Campsis radicans L. extracts and its aim is to investigate the antioxidant and antiproliferative effects of these extracts on the human colon adenocarcinoma cell line (HT-29). Cytotoxic activity in the HT-29 cell line was evaluated, and the 3-dimensional structures of phenolic compounds were obtained using the GC-MS method. Docking simulations were performed with AutoDock Vina, targeting proteins that are crucial in the apoptotic pathway (Bax, Bcl-2, and Caspase-3). Drug similarities and ADMET estimates of the phenolic compounds were obtained from databases. The highest antioxidant activity of Campsis radicans L. plant was observed in ethanol and water extracts, with notable inhibition capacities. While the total phenolic content was highest in ethanol, water, and ether extracts respectively the total flavonoid content was highest in ethanol, then ether, and water extracts. Certain elements were undetectable in mineral determination, and others exceeded the toxic doses for plants. The water extract exhibited dose-dependent cytotoxic activity in the HT-29 cell line, with an IC50 value of 4.47 mg/mL. Molecular docking results revealed the binding of phenolic molecules to the active sites of apoptotic pathway proteins. The findings suggest that Campsis radicans L. plant possesses cytotoxic properties, significant phenolic and flavonoid content, and a high antioxidant capacity. These properties make it a potential candidate for treatment use, emphasizing its potential therapeutic value in the HT-29 cell line. Further research and exploration on the identified phenolic compounds could contribute to the development of novel therapeutic agents.

Recurrent Pregnancy Loss (RPL) affects 1-2% of women, and its triggering factors are unclear. Several studies have shown the vaginal, endometrial, and gut microbiota may play a role in RPL. A decrease in the quantity of Lactobacillus crispatus in local microbiota has been associated with an increase in local (vaginal and endometrial) inflammatory response and immune cell activation that leads to pregnancy loss. The inflammatory response may be triggered by gram-negative bacteria, lipopolysaccharides (LPS), viral infections, mycosis, or atypia (tumor growth). Bacterial structures and metabolites produced by microbiota could be involved in immune cell modulation and may be responsible for immune cell activation and molecular mimicry. Gut microbiota metabolic products may increase the amount of circulating pro-inflammatory lymphocytes, which, in turn, will migrate into vaginal or endometrial tissues. Local proinflammatory Th1 and Th17 subpopulations along with a decrease in Treg and tolerogenic NK cells are accountable for the increase in pregnancy loss. Local microbiota may modulate the local inflammatory response increasing pregnancy success. Analyzing local and gut microbiota may be necessary to characterize some RPL patients. Although oral supplementation of probiotics has not been shown to modify vaginal or endometrial microbiota, the metabolites produced by it may benefit patients. Lactobacillus crispatus transplantation into the vagina may enhance the required immune tolerogenic response to achieve a normal pregnancy. The effect of hormone stimulation and progesterone to maintain early pregnancy on microbiota has not been adequately studied, and more research is needed in this area. Well-designed clinical trials are needed to ascertain the benefit of microbiota modulation in RPL.

Esophageal cancer (EC) is one of the most common malignant tumors worldwide, and its two major types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) present a severe global public health problem with an increasing incidence and mortality. Established risk factors include smoking, alcohol consumption, and dietary habits, but recent research highlights the substantial role of oral microbiota in EC pathogenesis. This review explores the intricate relationship between microbiome and esophageal carcinogenesis, focusing on eight significant mechanisms: chronic inflammation, microbial dysbiosis, production of carcinogenic metabolites, direct interaction with epithelial cells, epigenetic modifications, interaction with gastroesophageal reflux disease (GERD), metabolic changes, and angiogenesis. Certain harmful bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are specifically implicated in sustaining irritation and tumor progression through pathways including NF-κB and NLRP3 inflammasome. Additionally, the review explores how microbial byproducts, including short-chain fatty acids (SCFAs) and reactive oxygen species (ROS), contribute to DNA harm and disease advancement. Furthermore, the impact of reflux on microbiota composition and its role in esophageal carcinogenesis is evaluated. By combining epidemiological data with mechanistic understanding, this review underscores the potential to target microbiota-immune system interplay for novel therapeutic and diagnostic strategies to prevent and treat esophageal cancer.

Berberis vulgaris L. (Berberidaceae) is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of antiproliferative action of the plant’s methanolic root extract (BVR) against colon cancer cells. Cytotoxicity and pro-apoptotic activity were determined in human colon adenocarcinoma cell lines (LS180 and HT-29) and control colon epithelial CCD841 CoN cells. According to the MTT assay, after 48 h of cell exposure, the IC50 values were as follows: 4.3; 46.1 and 50.2 µg/mL for LS180, HT-29, and CCD841 CoN cells, respectively, showing the greater sensitivity of cancer cells to BVR. The Cell Death Detection ELISAPLUS kit demonstrated that BVR induced programmed cell death only against HT-29 cells. RT-qPCR with relative quantification method showed significant changes in the expression of genes related to apoptosis in both colon cancer cell lines. The genes BCL2L1 (126.84-366.66%), BCL2L2 (277.08-330.12%), CASP3 (180.36-261.36%) and CASP9 (158.08-213.46%) had significantly elevated expression, while BCL2 (23.08-52.06%) had reduced expression. Furthermore, in a panel of antioxidant tests, BVR showed positive effects (63.93±0.01, 122.92±0.01, and 220.29±0.02 mg Trolox equivalents (TE)/g in the DPPH•, ABTS•+ and ORAC assays, respectively). In the lipoxygenase (LOX) inhibition test, BVR revealed 62,60±0.87% of enzyme inhibition. The chemical composition of BVR was determined using UHPLC-UV-CAD-MS/MS analysis and confirmed the presence of several known alkaloids, including berberine, as well as other alkaloids and two derivatives of hydroxycinnamic acid (ferulic and sinapic acid hexosides). This is the first such extensive assessment of the biological activity of BVR. The results are very promising and encourage for the use of BVR as a comprehensive chemopreventive agent (anti-inflammatory, antioxidant, and pro-apoptotic) in colorectal cancer.

Background: Inhalation exposure to carcinogenic metals like cadmium (Cd) is a significant global health concern linked to various cancers. However, understanding their precise carcinogenic mechanism remains elusive. Methods: Using the colon cancer (CC) rat model and implanted intestinal stent, exposed them to atomized oxygen and nitrogen (O2/N2) gas containing Cd. Results: Atmospheric Cd intensified inflammation in CC cells, heightening nicotinamide adenine dinucleotide phosphate 1 (NOX1) activity, generating increased reactive oxygen species (ROS). This escalated ROS production triggered abnormal Wnt protein secretion, activating the Wnt/β-catenin pathway, stimulating CC cell proliferation. No discernible body weight effect was seen in CC mice, possibly due to later-stage tumor weight gain, masking rat changes. Cd facilitated colon tumor restructuring and cell migration later. Intestinal stents inhibited superoxide dismutase 1 (SOD1) in CC mice's tumors, with no clear effects on NOX1, SOD2, and catalase (CAT) enzymes. Elevated ROS levels didn't substantially impact Wnt/β-catenin and might slow its imbalance. Stent implantation eased inflammation, reducing CC cell proliferation but induced discomfort in rats, reducing food intake and weight. Conclusion: Cd might partially foster CC tumorigenesis via the ROS-mediated Wnt/β-catenin pathway. The effect of Cd on the invasive effect of intestinal stents in cancerous colon was not significant.

Cancer cells require substantial amounts of energy and substrates for their metabolic hyperactivity, enabling the synthesis of new cells at the expense of healthy ones. Preliminary in vitro data suggest that a mix of free essential amino acids (EAA-mix) can promote cancer cell apoptosis by enhancing autophagy. This study aimed to confirm, both in vitro and in vivo, whether EAA intake could influence the development of colon cancer in mice. We investigated changes in cancer proliferation in CT26 cells treated with EAA-mix, and in mice fed with EAA rich modified diets (EAARD) as compared to those on a standard laboratory diet (StD). CT26 cells were injected subcutaneously (s.c.) or intraperitoneally (i.p.). After 21 days, tumors were removed and measured. In vitro data corroborated that EAA-mix impairs cancer growth by inducing autophagy and apoptosis. In vivo data revealed that mice on StD developed significantly larger (s.c.) and more numerous (i.p.) cancers than those on EAARD. EAA administration appears to influence cancer cell survival with notable anti-proliferative properties.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

Plants significantly shape root-associated microbiota, making rhizosphere microbes useful environmental indicator organisms for safety assessment. Here, we report the pyrosequencing of the bacterial 16S ribosomal RNA in rhizosphere soil samples collected from transgenic cry1Ab/cry1Ac Bt rice Huahui No. 1 (GM crop) and its parental counterpart, Minghui63. We identified a total of 2,579 quantifiable bacterial operational taxonomic units (OTUs). Many treatment-enriched microbial OTUs were identified, including 14 NonGM-enriched OTUs and 10 GM-enriched OTUs. The rhizosphere microbiota communities were influenced more strongly by growth in the field than by rice varieties. Furthermore, Huahui No. 1 transgenic Bt rice had a greater impact on the rhizosphere bacterial communities than Minghui63. Early developmental stages of the transgenic Bt rice had a significant impact on many Bacillaceae communities. While soil chemical properties were not significantly altered by the presence of transgenic Bt rice, we found peak expression level of Bt proteins during the seedling stage, which may be an intriguing factor for bacterial diversity variations. Based on these findings, we conclude that transgenic Bt rice has a significant impact on root-associated bacteria. This information may be leveraged in future environmental safety assessments of transgenic Bt rice varieties.

The prospect of drinking water serving as a conduit for gut bacteria, artificially selected by disinfection strategies and lack of monitoring at the point of use, is concerning. Certain opportunistic pathogens, notably some nontuberculous mycobacteria (NTM), often exceed coliform bacteria levels in drinking water, posing safety risks. NTM and other microbiota resist chlorination and thrive in plumbing systems. When inhaled, opportunistic NTM can infect the lungs of immunocompromised or chronically ill patients, and the elderly, primarily postmenopausal women. When ingested with drinking water, NTM often survive stomach acidity, reach the intestines, migrate to other organs using immune cells as vehicles, potentially colonizing tumor tissue, including in breast cancer. The link between the microbiome and cancer is not new, yet the recognition of intratumoral microbiomes is a recent development. Breast cancer risk rises with age, and NTM infections emerged as a concern among breast cancer patients. In addition to studies hinting at a potential association between chronic NTM infections and lung cancer, NTM have also been detected in breast tumors at levels higher than normal adjacent tissue. Evaluating the risks of continued ingestion of contaminated drinking water is paramount, especially given the ability of various bacteria to migrate from the gut to breast tissue via entero-mammary pathways. This underscores a pressing need to revise water safety monitoring guidelines and delve into hormonal factors, which includes addressing the disproportionate impact of NTM infections and breast cancer on women and examining the potential health risks posed by the cryptic and unchecked microbiota from drinking water.

Objective: Mechanical bowel preparation is essential for the visualisation of the colon during colonoscopy, and previous studies have identified changes in gut microbiota composition after bowel preparation and colonoscopy. Considering the gut microbiota is increasingly implicated in mood, we aimed to explore the potential impact of this intervention on mood and the microbiota-gut-brain axis. Methods: We conducted a pre-post intervention study, with timepoints of one week before and one month after bowel preparation and colonoscopy, in community-dwelling adults referred for colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores using generalised estimating equations. We also examined changes in average anxiety, stress, and quality of life scores, and faecal microbiota composition and potential function using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and the gut microbiota and conducted post-hoc analyses to explore potential effect modifiers. Key Results: 59 participants were included in the analyses. Depressive symptoms decreased one-month post-procedure compared to baseline (adjusted β=−0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (1.78; 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Changes in gut microbiome composition included reduced alpha diversity, modest effects on beta-diversity, and increases in genera associated with potential health benefits, one-month post-procedure compared to baseline. Increases in the CLR-transformed abundance of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. Conclusions: There is preliminary evidence of a potential mental health effect of bowel preparation and colonoscopy, which may be associated with changes to the gut microbiota. There may also be a differential mental health impact of this procedure for those with and without IBS. Considering the limitations of our study, further research is required to confirm these findings and their clinical relevance.

A great deal of studies have assessed the expression of noncoding RNAs (ncRNAs) as well as their relevant molecular functions and biological mechanisms in the individuals of alcohol dependence. Alcohol dependence is one of the most prevalent neuropsychological disorders worldwide, and its pathogenesis is intricate and inadequately understood. There is considerable evidence demonstrating substantial links between multiple genetic factors and the development of alcohol dependence. Critical roles of ncRNAs have been emphasized in the pathophysiology of mental diseases including alcohol dependence. In the comprehension of ncRNAs action and their mechanisms of modification, they have emerged as therapeutic targets for a variety of psychiatric illness including alcohol dependence. Worth mentioning, dysregulated expression of ncRNAs has been regularly detected in individuals of alcohol dependence. An in-depth knowledge of roles of ncRNAs and m6A modification may be valuable for the development of a novel treatment against alcohol dependence. In general, a deeper comprehension of functional roles ncRNAs may make significant contributions to the precise diagnosis and/or actual treatment of alcohol dependence. Here in this review, we mostly focused on the up-to-date knowledge regarding alterations and/or modifications in the expression of ncRNAs in alcohol dependence, and then, presented their prospects for future research and therapeutic application with a novel concept of engram-system.

Antibiotic resistance is a global health problem. The human gut microbiome is implicated in the dynamics of antibiotic resistance acquisition and transmission, with the gut microbiota thought to play a crucial role. This study aimed to determine the potential influence of human gut bacteria microbiota on the gut resistome and the relationship between gut background microbiota and Escherichia coli resistome. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was used to systematically review studies that characterised gut microbiota and resistome using metagenomic analysis and/or those that reported gut E. coli resistome in healthy individuals. Changes in the diversity and abundance of bacterial gut microbiota and the resistome across different groups and the microbiota composition of the gut harbouring antibiotic-resistant E. coli were summarised. Findings suggest that lower bacterial microbiota diversity is likely associated with an increased abundance of the overall gut resistome. Age-related differences were observed, with younger infants exhibiting lower microbiota diversity and higher ARG abundance compared to older infants and adults. Studies that reported correlation revealed positive correlations between the compositional relative abundance of Proteobacteria and ARGs abundance, mainly driven by members within the Enterobacteriaceae family, particularly E. coli. This study also revealed that human gut microbiome studies that investigate gut resistome using metagenomic sequencing approaches in apparently healthy individuals are at least uncommon.

Lung and colon cancers are among the leading causes of cancer-related mortality worldwide. Early and accurate detection of these cancers is crucial for effective treatment and improved patient outcomes. False or incorrect detection is more harmful. Accurately detecting cancer in a patient's tissue is crucial to their effective treatment. While analyzing tissue samples is complicated and time-consuming, deep learning techniques have made it possible to complete this process more efficiently and accurately. As a result, researchers can study more patients in a shorter amount of time and at a lower cost. Much research has been conducted to investigate deep learning models that require great computational ability and resources. However, None of these have had a 100% accurate detection rate for these life-threatening malignancies. Misclassified or falsely detecting cancer can have more harmful consequences. This research proposes a new lightweight, parameter-efficient, and mobile-embedded deep learning model based on a 1D convolutional neural network with Squeeze-and-Excitation layers for efficient lung and colon cancer detection. This proposed model diagnoses and classifies lung squamous cell carcinomas and adenocarcinoma of the lung and colon from digital pathology images. Extensive experiment demonstrates that our proposed model achieves 100% accuracy for detecting lung, colon, and lung and colon cancers from the histopathological (LC25000) lung and colon datasets, which is considered the best accuracy for around 0.35 million trainable parameters and around 6.4 million flops. Compared with the existing results, our proposed architecture shows state-of-the-art performance in lung, colon, and lung and colon cancer detection.

This study aimed to determine the impact of a novel formulation of a supplement composed of the natural ingredients: bromelain, quercetin, and Lentinula edodes, on the gut microbiota of healthy adult dogs. Adult healthy female dogs were administered either a placebo (CTR, n = 15) or the supplement (TRT, n=15) over 28 days. Stool samples were collected for 16S rRNA sequencing before supplement administration (T0), at completion of supplement administration (T28), and one week after the end of supplement administration (T35) to characterize changes in the gut microbial communities. QIIME was used to determine both alpha- and beta-diversity and ANCOM-BC was used to identify differences in taxonomic abundances before and after supplementation. We found a significant decrease in overall diversity in CTR group, but no significant differences in overall diversity in the TRT group over time. Furthermore, we found differences in the abundance of several taxa in both CTR and TRT groups but differences in abundance of beneficial bacteria were more pronounced in TRT group. Specifically, we found increases in the abundance of sequences belonging to the genera Bifidobacterium, Lactobacillus, and Pediococcus at T28 in the TRT group with significant increases in Bifidobacterium and Lactobacillus persisting at T35 when compared to T0. Importantly, members of these genera are known to be pro anti-inflammatory and associated with a healthy gut microbiota in dogs. The results of our study show the potential of our supplement to selectively enhance specific beneficial bacterial taxa, offering a targeted approach to modulating the gut microbiome without causing disruptions to the overall equilibrium.

The gut microbiota (GM) communicates with the brain via biochemical signaling constituting the gut-brain axis, which significantly regulates the body's physiological processes. The GM dysbiosis can impact the digestive system and the functioning of the central nervous system (CNS) linked to the onset of neurodegenerative diseases. In this review, the scientific data compiled from diverse sources primarily emphasizes the neuropathological characteristics linked to the accumulation of modified insoluble proteins (such as β-Amyloid peptides and hyperphosphorylated tau proteins) in Alzheimer’s Disease (AD) and the potential impact of gut microbiota (GM) on AD susceptibility or resilience. The specific GM profile of human beings may serve as an essential tool for preventing or progressing neurodegenerative diseases like AD. This review focuses mainly on the effect of gut microfauna on the gut-brain axis in the onset and progression of AD. The GM produces various bioactive molecules that may serve as proinflammatory or anti-inflammatory signaling, contributing directly or indirectly to the repression or progression of neurodegenerative disorders by modulating the response of the brain axis. Human studies must focus on further understanding the gut-brain axis and venture to clarify microbiota-based therapeutic strategies for AD.

The nature of the relationship between the communities of microorganisms making up the microbiota in and on a host body has been increasingly explored in recent years. Microorganisms, including bacteria, archaea, viruses, parasites, and fungi, have often long co-evolved with their hosts. In human, the structure and diversity of microbiota vary according to the host’s immunity, diet, environment, age, physiological and metabolic status, medical practices (e.g. antibiotic treatment), climate, season, and host genetics. The recent advent of next generation sequencing (NGS) technologies enhanced observational capacities and allowed for a better understanding of the relationship between distinct microorganisms within microbiota. The interaction between the host and their microbiota has become a field of research into microorganisms with therapeutic and preventive interest for public health applications. This review aims at assessing the current knowledge on interactions between prokaryotic and eukaryotic communities. After a brief description of the metagenomic methods used in the studies analysed, we summarise the findings of available publications describing the interaction between the bacterial communities and protozoa, helminths, and fungi, either in vitro, in experimental models, or in humans. Overall, we observed the existence of a beneficial effect in situations where some microorganisms can improve the health status of the host, while the presence of other microorganisms has been associated with pathologies, resulting in an adverse effect on human health.

Polycystic ovary syndrome (PCOS) is a complex disorder that impacts both the endocrine and metabolic systems. The gut microbiota plays a crucial role in in metabolism regulation and immune responses through its interaction with the external environment. This article explores the intricate interplay between intestinal flora and the pathogenesis of PCOS, focusing on the pivotal role of microbial metabolites, specifically short-chain fatty acids (SCFAs). SCFA levels in fecal and blood samples from women with PCOS (n=69) and healthy controls (n=18) were analyzed using Gas Chromatography-Mass Spectrometry (GC/MS) for precise measurement. The results revealed that women with PCOS exhibited a significant reduction in beneficial bacteria alongside a notable overgrowth of opportunistic microorganisms. An overproduction of acetic acid (AA) and valeric acid (VA) in fecal samples suggests a link between elevated SCFAs and the development of obesity and PCOS. Interestingly, AA in the bloodstream might offer a protective effect against PCOS by ameliorating key symptoms such as high body mass index (BMI), insulin resistance (IR), and chronic inflammation. This finding points to the potential therapeutic value of maintaining optimal AA levels in the blood. Although serum SCFA levels showed non-significant changes following metformin treatment, the normalization of AA in the gut underscores that metformin exerts a more pronounced effect locally within the gastrointestinal tract. This treatment also led to an increase in beneficial gut bacteria and a reduction in opportunistic pathogens, suggesting a restoration of gut microbial balance. Furthermore, the study identified the most effective model for predicting the success of metformin therapy, based on serum concentrations of butyric acid (BA) and VA, achieving a 91% accuracy rate, 100% sensitivity, and 80% specificity. These promising findings highlight the potential for developing targeted interventions and personalized treatments, ultimately improving clinical outcomes for women with PCOS.

Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn’s disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we will discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.

The yak (Poephagus grunniens) has evolved unique adaptations to survive the harsh environment of the Tibetan Plateau, while their gut microorganisms play a crucial role in maintaining the health of the animal. Gut microbes spread through the animal population not only by horizontal transmission but also vertically, which enhances microbial stability and inheritance between generations of the population. Homogenization of gut microbes in different animal species occurs in the same habitat enhancing interspecies coexistence. Using the yak as a model animal, this paper reviews the adaptive strategies under extreme environments and how the gut microbes of the yak circulate throughout the Tibetan Plateau system, which not only affects other plateau animals such as plateau pikas, but can also have a profound impact on the health of people. By examining the relationships between yaks and their gut microbes, this review provides new perspectives in understanding the adaptations of plateau animals and the stability of the ecosystem.

Gene expression data is key for the functional annotation of single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS). Expression and splicing quantitative trait loci (e/sQTLs) in normal colon tissue, such as those from the University of Barcelona and University of Virginia RNA sequencing project (BarcUVa-Seq) and the Genotype-Tissue Expression project (GTEx), are required to gain biological insight of colon-related diseases risk loci. Moreover, transcriptome-wide association studies (TWAS) rely on reference gene expression imputation panels in the tissue of interest to nominate susceptibility genes. Also, it is of high interest to study the relationships between genes in a network framework. For facilitating these analyses, we have updated and expanded the scope of the Colon Transcriptome Explorer (CoTrEx) to the version 2.0. This web-based resource provides exhaustive visualization and analysis of transcriptome-wide gene expression profiles of normal colon tissue from BarcUVa-Seq and GTEx. In addition to the integration of new datasets, CoTrEx 2.0 provides additional e/sQTLs sets, as well as gene expression prediction models and regulatory and co-expression networks. It is freely available at https://barcuvaseq.org/cotrex/. Overall, it is of high interest for researchers aiming to investigate the genetic susceptibility to colon-related complex traits and diseases.

Increasing population size and income growth are causing and increasing demand for food and protein of animal origin. Insects are an interesting alternative to conventional animal source proteins as they can convert by-products from the agricultural industry to biomass for commercial feed for livestock and potentially as a food source for human consumption. Microorganisms have been found to affect insects and can be accumulated via horizontal and vertical transmission. This study aimed to identify if the removal of egg- and substrate-associated microorganisms impact larval performance through the following parameters: development of biomass, final biomass, and the survival rate of house fly (Musca domestica) larvae. Four treatments were tested on substrate consisting of 10.81% alfalfa (Medicago sativa), 21.62% wheat bran (Triticum aestivum), and 67.57% water: (A) disinfected eggs and non-autoclaved substrate, (B) non-disinfected eggs and autoclaved substrate, (C) disinfected eggs and autoclaved substrate, and (D) a control without any removal of microbiota. The results showed a significant decrease in final biomass for the treatments with only disinfected eggs, only autoclaved substrate and both when comparing to the control, and a significant decrease in survival rate for B and D. Moreover, the development of biomass showed a significant difference between days within all treatments. Together this suggest that microorganisms of housefly eggs and the growth substrate plays an important role for growth, which is critical in commercial insect production. Further studies must be performed to examine these parameters in more commercially relevant substrates.

Abstract: Cancer cells are originated by normal cells and with those share the need to be fed. Metabolic reprogramming in cancer cells is not yet fully understood although there is a vast literature suggesting that huge amounts of both energy and substrates are require for synthesis of components of new neoplastic cells so that any macronutrient may be efficiently utilized. Recently, in vitro data show that EAA supplementation promoted colon cancer cells apoptosis by enhanced autophagy. Therefore, in this study we tested in vivo the effects of matched macronutrients standard laboratory diet (control) versus EAA rich modified diet (EAArmd) in mice injected with colon cancer cells. Results of the first set of 12 animals, 6 controls and 6 EAArmd-fed, showed that controls mice develop cancer volume cancers 5 times larger and heavier than EAArmd-fed. If confirmed, these results would open new scenarios for the cancer integrate therapies.

Coffee is one of the most widely consumed beverages in the world, with important repercussions on the health of the individual. Dysbiosis in the gut microbiota is implicated in the occurrence of numerous diseases, and knowledge of it has also proven to be of fundamental importance for the development of new therapeutic strategies. In this narrative review, we thoroughly investigated the link between coffee consumption and its effects on the gut microbiota and their consequences on human health. We have selected the most significant articles published on this very interesting link, with the aim of going deeper in the light of the latest evidence more and more about the relationship that links coffee consumption and its repercussions on the composition of the gut microbiota and on human health.

Contrary to popular belief, we have known for many years that the endometrium is not a sterile environment and is considered to be a low-biomass milieu compared to the vagina. Numerous trials and studies have attempted to establish a valid sampling method and assess its physiological composition, but no consensus has been reached. Many factors such as ethnicity, age and inflammation, can influence the microbiome. Moreover, it possesses a higher alpha-diversity and therefore contains more diverse bacteria than the vagina. For instance, Lactobacillus has been shown to be a predominant genus in the vaginal microbiome of healthy women. Consequently, even if a majority of scientists postulate that a predominance of Lactobacillus inside the uterus improves reproductive outcomes, vaginal contamination by these bacteria during sampling cannot be ruled out. Certain pathologies, such as chronic endometritis, have been identified as inflammation perpetrators that hinder the embryo implantation process. This pro-inflammatory climate created by dysbiosis of the endometrial microbiota could induce secondary inflammatory mediators via Toll-like receptors, creating an environment conducive to the development of endometriosis and even promoting carcinogenesis. However, studies to this day have focused on small populations. In addition, there is no clearly defined healthy uterine composition yet. At most, only a few taxa have been identified as pathogenic. As sampling and analysis methods become increasingly precise, we can expect the endometrial microbiota to be incorporated into future diagnostic tools and treatments for women’s health.

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

Plant-derived compounds have been historically used for the treatment of various diseases and an important source of several clinically useful anti-cancer agents. The Artemisia annua is known as a medicinal herb that is effective against cancer. Thus, the purpose of this study was to investigate whether ethanol extracts of Artemisia annua could increase an anti-cancer effect against LS174T cells. Our results show that Artemisia annua extracts (AAE) induces apoptosis through the regulation of mitochondria outer membrane potential. We demonstrate that apoptosis is induced by p53-dependent manner when cells were treated with Nutlin-3 (MDM2 inhibitor) and LY294002 (Akt inhibitor). In addition, the apoptotic effect was also observed in the p53-independent manner through pifithrin-α (p53 inhibitor) and celecoxib (COX-2 inhibitor) treatment. As in in vitro, AAE induced apoptotic effects and regulated apoptosis-related proteins in LS174T xenograft model. Taken together, these results suggest that Artemisia annua extracts exerts an anti-cancer effect through p53-independent manner, as well as p53-dependent manner by p53´ translocation in LS174T colon cancer cells.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the results of traditional immunosuppressive therapy are disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients would eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and there is increasing evidence that gut microbiota and bile acids play an important role in cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Understanding the gut microbiota-bile acid network and corresponding immune functions in PBC provides a new perspective for its treatment strategies. Therefore, we summarize the latest advancements in research of gut microbiota and bile acids in PBC and, for the first time, explore the potential of immune factors related to them as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

This study investigated the development of novel probiotic formulations specifically designed for rainbow trout aquaculture. The project evaluated the effects of two formulations containing potential probiotic strains isolated from rainbow trout itself. These effects were assessed on various parameters including growth performance, immune response, liver enzyme activity, gene expression related to immunity, and the composition of the bacterial gut microbiota in rainbow trout (Oncorhynchus mykiss). In a completely randomized experimental design, a total of 450 rainbow trout were randomly divided into 70-liter fiberglass tank. The study included six treatments of three replicates (n=18 tanks). Six dietary treatments were included (A) and (B) containing three strains of Pediococcus sp P15, Lactococcus lactis ml3, Weissella cibaria ml6 at two dosages (300 and 500 mg/kg), treatments (C) and (D) containing five strains of P. sp P15, L. lactis ml3, W. cibaria ml6, Enterococcus faecium E10 and Lactobacillus curvatus 13A at two dosages (300 and 500 mg/kg), a commercial probiotic (E) at 300 mg/kg, and a control group (F) without probiotics. Treatments of (A), (B) and (E) resulted in the highest final weights in compared to control group. Fish fed treatments (A) and (B) had the lowest FCR than other groups. Treatments (A) and (D) showed a significant increase in immunoglobulin M (IgM) concentration compared to other groups. The expression of tumor necrosis factor (TNF) was significantly lower in group (A) than the control. In contrast, the expression of interleukin 6 (IL6) and immunoglobulin T (IgT) was increased 4.4-fold and 41-fold, respectively, in group (A) compared to control group. Among the probiotic fed treatments, group (A) showed a significant higher number of lactic acid bacteria compared to other groups during the experiment. This study highlights the significant role of treatment (A) containing three strains of P. sp P15, L. lactis ml3, and W. cibaria ml6 at a dosage of 300 mg/kg as a potential probiotic product for the rainbow trout industry.

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies to a variety of factors which may allow the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the Microbiota. This latter is made by all bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all conditions influencing the gut microbiota and, therefore, affecting response to immunotherapy, iRAEs and their management in NSCLC patients. The investigation of the landscape of these biological events can allow novel insights for optimal management of NSCLC immunotherapy.

(1) Background:The objective of this study was to explorethe dynamic changes of gut microbiota in Simmental calves before weaning, and compared microbial composition and functionality differences between diarrhea and health calves; (2) Methods: Fourteen neonatal Simmental calves were divided into a health group (n = 8) and diarrhea group (n = 6). The rectal stool samples were collected from each calf on days 1, 3, 5, 7, 9, 12, 15, 18, 22, 26, 30, 35, and 40. The high-throughput sequencing analysis of the 16S rRNA gene V1–V9 region was conducted to explore the changes in gut microbiota over time in both groups and assess the influence of diarrhea on microbiota structure and function; (3) Results: E.coli, B.fragilis, and B.vulgatus were the top three bacterial species of pre-weaning Simmental calves.Meanwhile, the major functions of fecalmicrobiota included the “Metabolic pathways”,“Biosynthesis of secondary metabolites”,“Biosynthesis of antibiotics”, “Microbial metabolism in diverse environments”, and “Biosynthesis of amino acids”. For calves in health group, PCoA revealed that the bacterial profiles generated from days 1, 3, 5, 7, and 9 separated from days 15, 18, 22, 26, 30, 35, and 40. While the microbial profiles of calves on day 12 crossed with both clusters, suggesting that the dynamic changes of microbial structures with the increasing of ages. When compared the difference of the relative abundance of bacteria between calves in health and diarrhea groups, the results showed that the relative abundance of the beneficial L.johnsonii, F.prausnitzii, and Limosilactobacillus in the health group were significantly higher than those in the diarrhea group (p

Tumor to stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study we proposed to confirm or dismiss the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma <10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients had stroma-rich tumors, 4% stroma-poor tumors and 89.2%tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation of stroma proportion with tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma-tumor interaction has to be further elucidated.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and despite advances in treatment, survival rates are still low; therefore, the development of novel drugs is imperative. Acetylcorynoline (ACN) is derived from Corydalis ambigua. The effect of ACN on colon cancer is still unknown. Therefore, we investigated its potential effects. Our data showed that ACN inhibited cell viability and proliferation. Moreover, ACN induced apoptosis and cell cycle arrest by inhibiting cell growth. In the present study, we hypothesized that ACN regulates c-Myc through CNOT2 or MID1IP1. ACN reduced the protein expression of oncogenic genes, decreased c-Myc half-life, and rapidly inhibited the serum stimulation response. Moreover, knockdown of CNOT2 and MID1IP1 with ACN increased apoptosis and further reduced the expression of oncogenes. In addition, ACN exhibited a synergistic effect with low-dose of 5-fluorouracil (5-FU) and doxorubicin (Dox). Collectively, our data demonstrates that ACN inhibited c-Myc expression through CNOT2 and MID1IP1 and induced apoptosis. These findings indicate the potential of ACN as a therapeutic agent against colon cancer.

Animals form functional units with their microbial communities, termed metaorganisms. While extensive research has been conducted on a few model animals, much remains unknown about the microbial diversity in most species. Here, we describe the taxonomic profile of the microbes from the outer gut mucus layer from the Northeast Arctic cod or also called the migrating Atlantic cod using a shotgun DNA sequencing approach. We provide metagenomes from six individuals. The results reveal three different taxonomic profile “types": Type I is dominated in numbers by Pseudomonaceae (44%) and Xanthomonadaceae (13%), Type II contains 65% Vibrionaceae and Type III contains 76% Enterobacteriaceae. This stands in sharp contrast to the bacterial diversity of the transient gut content (i.e., feces). Additionally, binning of assembled reads followed by phylogenomic analyses place a high-completeness bin of Type I within the Pseudomonas fluorescens group, one bin of Type II within the Photobacterium phosphoreum clade, and finally a bin of Type III within the Escherichia/Shigella group. In conclusion, we describe the adherent bacterial diversity in the Northeast Arctic cod's intestine using shotgun sequencing, revealing different taxonomic profiles compared to the more homogenous transient (fecal) microbiota. This suggests that the intestine contains two separate and distinct microbial populations.

The microbioma is presently one of the hottest areas of scientific and medical research and exerts a marked influence on the host during homeostasis and disease. Fermented foods arise in the human relationship to the microbial environment. Further to the traditionally recognized effects of fermented foods and beverages on the digestive health and well-being there is now strong evidence on their general health benefits, namely the significance on the gut microbiota and brain functionality. We highlight the possibilities in this field, how little is still known, and call for a convergence of interdisciplinary research fields of One Health microbe-nutrition with fermented foods and gut-brain research. A consequence of civilisation, changes in present-day society in diets with more sugar, fat and salt, habits and lifestyle, contributes to the likelihood of an inflammatory microbiome, particularly the global epidemics of obesity and mental health. Although two recent papers claim that probiotics perturb rather than aid in microbiota recovery back to baseline after antibiotic administration in humans, consuming fermented foods has shown to reduce inflammation so improve gut health and the proper function of the body’s immune system.

The artificial solar saltwork fields of Hon Khoi are important industrial and biodiversity resources in southern Vietnam. Most hypersaline environments in this area are characterized by saturated salinity, nearly neutral pH, intense ultraviolet radiation, elevated temperatures and fast desiccation processes. However, the extreme halophilic prokaryotic communities associated with these stressful environments remain uninvestigated. To fill this gap, a metabarcoding approach was conducted to characterize these communities by comparing them with solar salterns in northern Vietnam as well as with Italian salterns. Sequencing analyses revealed that the multiple reuses of crystallization ponds apparently create significant perturbations and structural instability in prokaryotic consortia. However, some interesting features were noticed when we examined the diversity of ultra-small prokaryotes belonging to Patescibacteria and DPANN Archaea. Surprisingly, we found at least five deeply branched clades, two from Patescibacteria and three from DPANN Archaea, which seem to be quite specific to Hon Khoi saltwork fields ecosystem and can be considered as a part of biogeographical connotation. Further studies are needed to characterize these uncultivated taxa, to isolate and cultivate them, which will allow us to elucidate their ecological role in these hypersaline habitats and to explore their biotechnological and biomedical potential.

Colon cancer (CRC) is a prevalent malignancy that exhibits distinct differences in incidence, prognosis, and treatment responses between males and females. These disparities have long been attributed to hormonal differences, particularly the influence of estrogen signaling. This review aims to provide a comprehensive analysis of recent advances in our understanding of the molecular mechanisms underlying sex differences in colon cancer and the protective role of membrane and nuclear estrogen signaling in CRC development, progression, and therapeutic interventions. We discuss the epidemiological and molecular evidence supporting sex differences in colon cancer, followed by an exploration of the impact of estrogen in CRC through various genomic and non-genomic signaling pathways involving membrane and nuclear estrogen receptors. Furthermore, we examine the interplay between estrogen receptors and other signaling pathways, in particular the Wnt/-catenin proliferative pathway and hypoxia in shaping biological sex differences and estrogen protective actions in colon cancer. Lastly, we highlight the potential therapeutic implications of targeting estrogen signaling in the management of colon cancer and propose future research directions to address the current gaps in our understanding of this complex phenomenon.

Congenital Pouch Colon (CPC) is a rare anorectal anomaly common to North Western India specifically Rajasthan. Despite efforts to understand the clinical genetic makeup of CPC, no attempt on identifying non-coding RNAs was done. We have earlier reported CPC's rare variants from whole exome sequencing across 18 affected samples in a total of 64 subjects. A Smith-Waterman algorithm was used to infer a couple of lncRNAs from WES samples of CPC with predictions from the Noncode database. Further screening and quantification using PCR, we ascertained interactions using Micro Scale Thermophoresis (MST). We report the role of lnc-EPB41-1-1 shown to be promiscuously interacting with KIF13A substantiating their role in regulation.

Collision tumors, even uncommon, characterized by two distinctive (morphological, as well immunohistochemical) and spatially independent tumor components in the same location, are always puzzling for clinicians, pathologists and patients because they don’t fit in usual approaching schemes, neither diagnostic, nor therapeutic. Reviewing the specialized literature, until now, collision tumors have been reported in multiple locations such as the skin, esophagus, stomach, liver, kidney, bladder, adrenal gland or thyroid. We report a case of coexistence on the same site of a malignant tumor of ascending colon and a benign one emerging from peritoneal lining, thought initially by the surgeon to be right sided serosal carcinomatosis. But the histopatological examination reveals that those multiple serosal nodules were benign granular cell tumors collided with highly aggressive transparietal signet-ring colon carcinoma. These results put the patient's prognosis and therapeutic strategy in a different light than the clinical-imaging and intraoperative assessment.

Tryptophan metabolism, via the kynurenine (Kyn) pathway, and microbial transformation of tryptophan to indolic compounds, are fundamental for host health; both of which are altered in colon carcinogenesis. Alterations in tryptophan metabolism begin early in colon carcinogenesis as an adaptive mechanism for the tumor to escape immune surveillance and metastasize. The microbial community is a key part of the tumor microenvironment and influences cancer initiation, promotion and treatment response. A growing awareness of the impact of the microbiome on tryptophan (Trp) metabolism in the context of carcinogenesis has prompted this review. We first compare the different metabolic pathways of Trp under normal cellular physiology to colon carcinogenesis, in both the host cells and the microbiome. Second, we review how the microbiome, specifically indoles, influence host tryptophan pathways under normal and oncogenic metabolism. We conclude by proposing several dietary, microbial and drug therapeutic modalities that can be utilized in combination to abrogate tumorigenesis.

Curcumin and trans-cinnamaldehyde are acrolein-based Michael acceptor compounds that are commonly found in domestic condiments, and known to cause cancer cell death via redox mechanisms. Based on the structural features of these compounds we designed and synthesized several 2-cinnamamido-N-substituted-cinnamamide (bis-cinnamamide) compounds. One of the derivatives, (Z)-2-[(E)-cinnamamido]-3-phenyl-N-propylacrylamide 1512 showed a moderate antiproliferative potency (HCT-116 cell line inhibition of 32.0 µM), good selectivity profile (no inhibition of normal cell lines), and proven cellular activities leading to apoptosis. SAR studies led to more than 10-fold increase in activity. Our most promising compound, [(Z)-3-(1H-indol-3-yl)-N-propyl-2-[(E)-3-(thien-2-yl)propenamido)propenamide] 4112 killed colon cancer cells at IC50 = 0.89 µM (Caco-2), 2.85 µM (HCT-116) and 1.65 µM (HT-29), while exhibiting much weaker potency on C-166 and BHK normal cell lines (IC50 = 71 µM and 77.6 µM, respectively). Cellular studies towards identifying the compounds mechanism of cytotoxic activities revealed that apoptotic induction occurs in part as a result of oxidative stress. Importantly, the compounds showed inhibition of cancer stem cells that are critical for maintaining the potential for self-renewal and stemness. The results presented here show discovery of covalently-acting Michael addition compounds that potently kill cancer cells by a defined mechanism, with minimal effect on normal noncancerous cell.

Early detection of cancer increases the probability of recovery. This paper presents an intelligent decision support system (IDSS) for the early diagnosis of cancer based on gene expression profiles collected using DNA microarrays. Such datasets pose a challenge because of the small number of samples (no more than a few hundred) relative to the large number of genes (on the order of thousands). Therefore, a method of reducing the number of features (genes) that are not relevant to the disease of interest is necessary to avoid overfitting. The proposed methodology uses the information gain (IG) to select the most important features from the input patterns. Then, the selected features (genes) are reduced by applying the grey wolf optimization (GWO) algorithm. Finally, the methodology employs a support vector machine (SVM) classifier for cancer type classification. The proposed methodology was applied to two datasets (Breast and Colon) and was evaluated based on its classification accuracy, which is the most important performance measure in disease diagnosis. The experimental results indicate that the proposed methodology is able to enhance the stability of the classification accuracy as well as the feature selection

The body's billions of bacteria—the microbiota—influence health and illness. The microbiome—the genetic material of these microbes—affects digestion, immunological function, and mental health. Due to bacterial variety, complicated relationships, and research technique constraints, investigating the microbiota is difficult. AI and machine learning have expanded microbiome research. Artificial intelligence (AI) systems can efficiently scan large microbiome datasets to help researchers understand microbial populations and their functions. AI-based predictive algorithms can analyze food impacts on microbial communities and forecast illness risks based on gut microbiota composition. AI helps find microbial biomarkers linked to specific health disorders, enabling early illness identification and targeted therapy. AI-driven medication development platforms also modulate microbiome to treat microbiota-related diseases. Understanding microbial populations' involvement in health and illness requires understanding complicated microbial interactions within the microbiome and between it and the host. AI systems improve human health by comprehending these complex relationships. AI in microbiota study must overcome various obstacles. Data quality and AI model interpretability are essential for accurate findings. Diverse and representative datasets avoid biases and strengthen AI-driven conclusions. AI in microbiota research requires data protection, informed permission, and appropriate use of sensitive data. AI is improving our understanding of the human microbiome and its health effects, changing microbiota research. Overcoming difficulties and adhering to ethical norms will enable the proper use of AI-driven findings, leading to microbiome insights and precision medical breakthroughs.

The human body is inhabited by unique microbial communities that protect and regulate the host against pathogens and inflammation. To address issues related to disrupted microbial composition, microbial transfer therapy (MTT) has emerged as a potential treatment option. The most popular form of MTT is fecal microbiota transplantation (FMT), which has been successful in treating various diseases. Another emerging form of MTT is vaginal microbiota transplantation (VMT), transferring of the vaginal microbiota from a healthy female donor to a diseased patient's vaginal cavity, which aims to restore normal vaginal microbial composition. However, VMT is vastly unexplored due to safety concerns and lack of research. This paper explores the mechanisms involved in VMT's therapeutic effect and discusses future perspectives. Further research is needed to advance VMT's clinical applications and techniques.

Nutrition is crucial for the management of patients affected by chronic kidney disease (CKD) to slow down disease progression and to correct symptoms. The mainstay of the nutritional approach to renal patients is protein restriction coupled with adequate energy supply to prevent malnutrition. However, other aspects of renal diets, including fiber content, can be beneficial. This paper summarizes the latest literature on the role of different types of dietary fiber in CKD, with special attention to intestinal microbiota and the potential protective role of renal diets. Fibers have been identified based on aqueous solubility, but other features, such as viscosity, fermentability, and bulking effect in the colon should be considered. A proper amount of fiber should be recommended not only in the general population but also in CKD patients, to achieve an adequate composition and metabolism of intestinal microbiota and to reduce the risks connected with obesity, diabetes, and dyslipidemia.

New research points to a possible link between Autism Spectrum Disorder and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites or leaky gut in autistic people are described. Various altered metabolite levels were observed in autistic children, many of those were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides. A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients triggering new body responses or altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in the cells, altered tight junctions in the blood brain barrier and structural changes in cortex, hippocampus, amygdala and cerebellum were detected. Moreover, this paper suggests that autism is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between autism and gut microbiota is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health. Diagnostic and therapeutic value of new biomarkers leading to the perturbation in the phenylalanine metabolism will be discussed.

Obesity and chronic low-grade inflammation are becoming global epidemics. The dysbiosis has a specific role in the metabolism and energy stocks of the host. The discovery that a low-grade of inflammation could be directly connected to the intestinal microbiota metabolic endotoxemia (elevated levels of plasma lipopolysaccharides) has allowed the identification of novel mechanisms involved in the control of the intestinal barrier. In this review, it will analyze the latest news to explain how human symbiotic microorganisms participate in the growth of the fat reserves and promote insulin resistance as a low-grade inflammation. Besides, it will discuss new treatments with probiotics and prebiotics as a promising therapeutic approach to reverse the host's metabolic changes linked to dysbiosis observed in obesity.

Pigs are a social species and they stablish hierarchies for a better use of resources and to reduce conflicts. However, in pig production, the opportunities for growing can differ in dominant and subordinate animals. In the present study a system was tested to perform a Dominance versus Subordinate test in growing pigs to investigate how the hierarchy affects feeding behaviour, growth and gut microbiota assessed in faeces. 64 animals housed in eight different pens were used, with four castrated males and four females in each one, weighing 18kg at arrival and maintained during the whole growing period, until 140 kg. Three stool samplings were obtained from the animals directly from the anus to avoid contamination of the faeces on 58, 100 and 133 days after the start of the study to investigate the microbiota composition. The dominant animals had higher gains during the growing period that the subordinate. In addition, they were performing more visits to the feeder throughout the day. Differential abundance patterns were observed in five bacterial genera, Oliverpabstia, Peptococcus, and Faecalbacterium being more abundant in dominant animals and Holdemanella and Acetitomaculum being overrepresented in subordinate ones. This microbial biomarker accurately classified dominant versus subordinate groups of samples with an AUC of 0.92.

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.

In the present study the synthesis of gold nanoparticles (AuNPs) loaded with methotrexate (MTX) has been carried out in order to obtain controlled size and monodispersed nanocarriers, around 20nm. Characterization study shows metallic AuNPs with MTX polydispersed on the surface. MTX is linked by a replacement of citrate by the MTX carboxyl group. The drug release profiles showed faster MTX release when it is conjugated, which leads to the best control of plasma concentration. Also, the enhanced release observed at pH 5 could take advantage of the pH gradients that exist in tumor microenvironments to achieve high local drug concentrations. AuNPs-MTX conjugates were tested by flow cytometry against lung (A-549) and colon (HTC-116) cancer cell lines. Results for A-549 showed a lighter dose-response effect than for colon cancer ones. This could be related to the presence of folate receptors in line HTC-116 on the contrary than line A-549, supporting the specific uptake of folate-conjugated AuNPs-MTX by folate receptor positive tumor cells. Conjugates exhibited considerably higher cytotoxic effects compared with the effects of equal doses of free MTX. Anexin V-PI test sustain as cell death mechanism apoptosis, which is normally disabled in cancer cells.

Palmitic acid metabolism involves delta-9 and delta-6 desaturase enzymes forming palmitoleic acid (9cis-16:1; n-7 series) and sapienic acid (6cis-16:1; n-10 series), respectively. The corresponding biological consequences and lipidomic research on these positional MUFA isomers are under development. Furthermore, sapienic acid can bring to the de novo synthesis of the n-10 polyunsaturated fatty acid (PUFA) sebaleic acid (5cis,8cis-18:2), but such transformations in cancer cells are not known. The model of Caco-2 cell line was used to monitor sapienic acid supplementation (150 and 300 μM) and evidence the formation of n-10 fatty acids as well as their incorporation at levels of membrane phospholipids and triglycerides. Comparison with palmitoleic and palmitic acids evidenced that lipid remodeling was influenced by the type of fatty acid and positional isomer, with increase of 8cis-18:1, n-10 PUFA and decrease of saturated fats in case of sapienic acid. Cholesteryl esters were formed only in case of sapienic acid. EC₅₀ of sapienic acid (232.3 μM at 96 hrs) was the highest found among the tested fatty acids, thus influencing cell viability that was only reduced at 25% at 300 μM, whereas palmitoleic acid induced cell death. Two-photon fluorescent microscopy with Laurdan as a fluorescent dye provided information on membrane fluidity, highlighting that sapienic acid increases the distribution of fluid regions, probably connected with the formation of 8cis-18:1 and the n-10 PUFA in cell lipidome. Our results bring evidence for MUFA positional isomers and de novo PUFA synthesis for developing lipidomic analysis and cancer research.

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.

The mammalian or mechanistic target of rapamycin (mTOR) integrates multiple intracellular and extra-cellular upstream signals involved in the regulation of anabolic and catabolic processes in cells, and plays a key regulatory role in cell growth and metabolism. Activation of the mTOR signaling pathway has been reported to be associated with a wide range of human diseases. A growing number of in vivo and in vitro studies have demonstrated that the gut microbes and its complex metabolites can regulate host metabolic and immune responses through the mTOR pathway, and result in disorders of host phys-iological functions. In this review, we summarize the regulatory mechanisms of gut microbes and mTOR in different diseases, and discuss the crosstalk between gut microbes and their metabolites and mTOR in the disorders in gastrointestinal tract, liver, heart and other organs. We also discuss the promising appli-cation of multiple potential drugs that can adjust the gut microbiota and mTOR signal pathways. Despite the limited findings between gut microbes and mTOR, elucidating their relationship may provide new clues for the prevention and treatment of various diseases.

Equine fecal microbiota transplantation (FMT) is an emerging therapy for restoring gut microbiome balance in horses. An imbalance in the gut microorganisms, known as dysbiosis, can cause inflammation and metabolic disruptions. FMT, which involves transferring gut bacteria from a healthy donor to a diseased recipient, has shown positive results in treating gastrointestinal diseases in horses, but is still largely limited to research purposes due to safety concerns and lack of understanding of its mechanisms. This paper aims to shed light on the possible mechanisms of FMT in horses and discuss future perspectives for its clinical application. Further research is needed to develop more effective and safer FMT techniques for horses.

Fecal microbiota transplantation (FMT) is an emerging therapeutic option for a variety of diseases, which is characterized as transferring fecal microorganisms from a healthy donor into the intestinal tract of a diseased receipt. In human clinics, FMT has been used for treating diseases for decades with promising results. In recent years, veterinary specialists adapted FMT in canine patients, however, compared to humans, canine FMT is more inclined to research purposes than practical applications in most cases due to safety concerns. Therefore, in order to facilitate the application of fecal transplant therapy in dogs, in this paper, we aimed to review recent application of FMT in canine clinical treatments as well as possible mechanisms that are involved in the process of therapeutic effect of FMT.

Gestational diabetes (GDM) is considered a significant and increasing problem worldwide. The growing body of evidence points out that a hostile intrauterine environment in mothers with GDM via epigenetic mechanisms induces "diabetogenic" and "obesogenic" changes in an offspring's DNA. This sets in motion a vicious intergenerational cycle of metabolic diseases gradually deteriorating the health of the human population. One of the most important players in this process seems to be altered microbiota/microbiome. There is a chance that the identification of specific epigenetic marks may provide a key for future diagnostic, prognostic and therapeutic solutions/measures in the field of person-alized medicine. Given the reversibility of most epigenetic changes, an opportunity arises to improve the long-term health of the human population/race. In this manuscript, we aim to summarize available data on epigenetic changes among women suffering from GDM and their progeny in association with changes in microbiome.

ERK1/2 phosphorylation is frequently downregulated in the early phase of colon tumorigenesis with subsequent activation of ERK5. In the current work, we studied the advantage of ERK1/2 downregulation for tumor growth by dissecting the individual functions of ERK1 and ERK2. The patient sample data demonstrated decreased ERK1/2 phosphorylation in the early phase of tumorigenesis followed by upregulation of the phosphorylation in late-stage colon adenocarcinomas with intratumoral invasion or metastasis. In vitro results indicated SOD3-mediated coordination of small GTPase RAS regulatory genes in the inhibition of RAS-ERK1/2 signaling. In vitro and in vivo studies suggested that ERK2 has a more prominent role in chemotactic invasion, collective migration, and cell proliferation than ERK1. Noteworthily, simultaneous ERK1 and ERK2 expression inhibited collective cell migration and proliferation but tended to promote invasion, therefore suggesting that ERK1 controls ERK2 function. According to the present data, phosphorylated ERK1/2 at the early phase of colon adenocarcinoma limits tumor mass expansion, whereas reactivation of the kinases at the later phase of colon carcinogenesis is associated with the initiation of metastasis. Additionally, our results suggest that ERK1 is a regulatory kinase, which coordinates ERK2-promoted chemotactic invasion, collective migration, and cell proliferation. Our findings indicate that ROS, especially H2O2, are associated with the regulation of ERK1/2 phosphorylation in colon cancer either increasing or decreasing the kinase activity. The data suggesting a growth-promoting role for ERK2 and a regulatory role for ERK1 could result in new avenues in the developmental strategies for cancer therapy.

BMAP-27 peptide known to exert cytotoxic effects against cancer cells by membrane integrity disruption. In the current investigation, we aimed to study the role of the BMAP-27 peptide in reducing colon cancer cell proliferation and inducing apoptosis. This study utilized both primary and metastatic colon cancer cell lines (SW480 and SW620). Proliferation was measured using CCK-8, and cellular damage was analyzed by lactate dehydrogenase assay. The study assessed apoptosis, cell cycle, and proliferation by measuring the expression of CASPASE3, BAX, BCL-2, TP53, CDK-6, PCNA, Wnt11, AXIN1, and CTNNB1. Additionally, in-silico studies were conducted to determine the binding affinities of BMAP-27 with APC and β-catenin proteins. BMAP-27 peptide reduced colon cancer cell proliferation, upregulated CASPASE3, BAX, TP53, AXIN1 expression, and downregulated BCL-2, CDK-6, PCNA, WNT11, CTNNB1 in both colon cancer cell lines, however, demonstrated higher activity in primary than metastatic colon cancer cells. The molecular dynamic simulation revealed substantial binding affinity of the peptide to adenomatous polyposis coli and β-catenin proteins.BMAP-27 peptide effectively inhibited the proliferation and enhanced apoptosis in the primary than in metastatic colon cancer cells. In-silico findings suggest that BMAP-27 exhibits a strong binding affinity with APC and β-catenin, highlighting its potential role as an anti-colon cancer agent.

Hepatocellular carcinoma (HCC), one of the leading causes of death worldwide, has a causal nexus with liver injury, inflammation, and regeneration that accumulate over decades. Observations from recent studies have accounted for the involvement of the gut-liver axis in the pathophysiological mechanism responsible for HCC. The human intestine nurtures a diversified colony of microorganisms residing in the host ecosystem. The intestinal barrier is critical for conserving the normal physiology of the gut microbiome. Therefore, a rupture of this barrier or dysbiosis cause the intestinal microbiome to serve as the main source of portal-vein endotoxins such as lipopolysaccharide, in the progression of hepatic diseases. Indeed, increased bacterial translocation is a key sign of HCC. Considering the limited number of clinical studies on HCC with respect to the microbiome, we focus on the clinical as well as animal studies involving the gut microbiota with the current understandings of the mechanism by which the intestinal dysbiosis promotes hepatocarcinogenesis. Future research might offer mechanistic insights into the specific phyla targeting the leaky gut, as well as microbial dysbiosis, and their metabolites, as key pathways that drive HCC-promoting microbiome-mediated liver inflammation and fibrosis, thereby restoring the gut barrier function.

Accumulating evidence suggests that metformin, used as an antidiabetic drug, possesses anticancer properties. Metformin reduced the incidence and growth of experimental tumors in vivo. In a randomized clinical trial among nondiabetic patients, metformin treatment significantly decreased the number of aberrant crypt foci compared to the untreated group with a follow-up of 1 month. In our study, HT29 cells were treated with graded concentrations of metformin, 10 mM/25 mM/50 mM, for 24/48 hours. We performed immunofluorescence experiments by means of confocal microscopy and Western blot analysis to evaluate a panel of factors involved in apoptotic/autophagic processes and oxidative stress response. Moreover, HT29 cells treated with metformin were analyzed by flow cytometry assay to detect the cell apoptosis rate. The results demonstrate that metformin exerts growth inhibitory effects on cultured HT29 cells by increasing both apoptosis and autophagy; moreover, it affects the survival of cultured cells inhibiting the transcriptional activation of nuclear factor E2–related factor 2 (NRF-2) and nuclear factor–kappa B (NF-κB). The effects of metformin on HT29 cells were dose- and time-dependent. These results are very intriguing, since metformin is emerging as a multifaceted drug: it has a good safety profile and is associated with low cost, and it might be a promising candidate for the prevention or treatment of colorectal cancer.

Decompression sickness (DCS) with neurological disorders is the leading cause of diving accidents. Exposure to high levels of CO2 during diving is a safety concern for occupational , groups at risk of DCS. However, the effects of prior exposure to CO2 have never been evaluated. The purpose of this study was to evaluate the effect of CO2 breathing prior to a provocative dive on the occurrence of DCS in mice. 50 mice were exposed to a maximum CO2 concentration of 70 hPa for one hour at atmospheric pressure. Another 50 mice breathing air under similar conditions served as controls. In the AIR group (controls), 22 out of 50 mice showed post-dive symptoms compared to 44 out of 50 in the CO2 group. We found that CO2 breathing is associated with a decrease in body temperature in mice and that CO2 exposure dramatically increases the incidence of DCS. More unexpectedly, it appears that a lower temperature of the animals even before exposure to the accident-prone protocol leads to an unfavorable prognosis. This study also suggests that the composition of the microbiota may influence thermogenesis and thus accidentology. Depending on prior exposure, some bacteria identified in this work could be perceived as protective or pathogenic.

Adolescents most often experience mild acute COVID-19 but may still face fatigue and persistent symptoms such as post-COVID-19 condition (PCC) and post-infective fatigue syndrome (PIFS). We explored the fecal microbiota in a prospective controlled cohort of 136 non-hospitalized SARS-CoV-2-positive and 32 SARS-CoV-2-negative controls aged 12–25 years. With a targeted qPCR approach, the quantities of 100 fecal bacterial taxa were measured at baseline (early convalescent stage) and after six months. Results: Faecalibacterium prausnitzii M21.2 and Gemmiger formicilis (both p&lt;0.001) were enriched in the SARS-CoV-2-positive participants compared to controls at baseline. Lower baseline abundance of Faecalibacterium prausnitzii M21/2 (p=0.013) and higher abundance of Clostridium spiroforme (p=0.006), Sutterella wadsworthensis (p&lt;0.001) and Streptococcus thermophilus (p=0.039) were associated with six-month fatigue. Sutterella wadsworthensis and Streptococcus thermophilus enrichment was additionally associated with PCC in the SARS-CoV-2-positive group (p&lt;0.001 and 0.042 respectively). Conclusions: In mild SARS-CoV-2 infection in adolescents and young adults, beneficial Faecalibacterium prausnitzii M21/2 and Gemmiger formicilis were enriched compared to SARS-CoV-2 negative controls. Additionally, both known (Faecalibacterium prausnitzii, Streptococcus thermophilus) and new (Clostridium spiroforme, Sutterella wadsworthensis) bacteria were associated with persistent symptoms in the COVID-19 infected group, warranting further exploration of the role of these bacteria in COVID-19 disease and PCC pathophysiology.

Colon cancer (CC) is one of the leading causes of cancer-related death worldwide. Gene hypermethylation is a well-known alteration that contributes to tumour progression in CC. It is essential to analyse new molecular markers that can delineate more aggressive CC cases. The detection of new epigenetic alterations such as hypermethylation and hypomethylation of regulatory gene regions that participate in crucial mechanisms of cancer progression, such as epithelial mesenchymal transition (EMT), could be useful for identifying cases that might benefit from a closer follow-up by clinicians. In the present report we describe, for the first time, the hypermethylation of the ZEB1 gene, which is more frequent in cases without expression of hMLH1. More importantly, this epigenetic alteration is a good prognostic factor related to disease-free and overall survival in all cases and Consensus Molecular Subtypes (CMS2/3) independently of other clinical parameters such as patient age, stage, lymph node involvement, and blood vessel and perineural invasion.

The purpose of current research work was to formulate and typify gelatin and poly(vinyl) alcohol (Gel/PVA) hydrogel which would be highly pH-responsive and can able to accomplish targeted delivery of methotrexate in order to treat the colo-rectal pathologies. The primed gel/pva hydrogel discs were subjected to various physicochemical techniques i.e. swelling, diffusion co-efficient, sol-gel analysis and porosity using three altered sorts of pH (1.2, 6.8 & 7.4) phosphate buffer solutions for assessment/evaluation, and their characterization was done through Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA). Shape alteration and controlled methotrexate of release of Gel/PVA hydrogel have been done using three type of pH (1.2, 6.8 & 7.4) phosphate buffer mediums. Methotrexate was loaded through in-situ drug loading method due to hydrophobicity. Different kinetic models (first order & zero order kinetic), Higuchi model and Krosmere peppas model/Power law were applied to manipulate the drug release data. Physicochemical evaluation tests and drug release profile results were found insignificant (p< 0.05) in various pH mediums and dependent upon polymers concentration pH of medium and cross-linker amount. Kinetic model disclosed that release of methotrexate from Gel/PVA hydrogel follow non-Fickian diffusion method. It became concluded from this research work that release of methotrexate Gel/PVA hydrogel in targeted colon area can be achieved for treating colo-rectal disorders.

miRNA sponges allow the selective blockade of a complete family of associated miRNAs which induce posttranscriptional gene silencing in its target through binding to 3´UTR mRNA. MiRNA-365 and miRNA-145 are down-regulated in colorectal cancer (CRC), but not in health tissues. Based on this, we constructed two vectors by inserting miRNA sponge (one for miRNA-365 and other for miRNA-145), and used EGFP (enhanced green fluorescent protein) as a 3′ UTR reporter gene to analyse the ability of each sponge to catch its respective miRNA. qPCR results corroborated that the expression levels of both miRNAs were lower in CRC cell lines than in normal colon cell line. Flow cytometry analysis revealed a decrease of the EGFP expression levels in the cell lines transfected with both sponges, being higher on the normal cell line while CRC cell lines presented a minimal decline. Also, this decrease was inversely proportional to the levels of expression of both miRNAs obtained by qPCR. These results were corroborated by fluorescence microscopy, showing a similar decrease fluorescence. We propose a new vector system to carry in a specific way the expression of genes to CRC cells without affecting healthy cells, preventing damage to healthy tissues.

The lung microbiota is a complex community of microorganisms that colonize the respiratory tract of individuals from or even before birth. Although the lungs were traditionally believed to be sterile, recent research has shown that there is a diversity of bacterial species in the respiratory system. Knowledge about the lung microbiota in the newborn and its relationship with bacterial infections is of vital importance to understand the pathogenesis of respiratory diseases in neona-tal patients undergoing mechanical ventilation. In this article, the current evidence on the compo-sition of the lung microbiota in the newborn will be reviewed, as well as its role in the develop-ment of bacterial infections in mechanically ventilated neonates. Although advances in many as-pects of the neonatal intensive care unit care have significantly improved the survival of preterm infants, the diagnosis and treatment of ventilator-associated pneumonia has not progressed in recent decades. Avoiding dysbiosis caused by inappropriate use of antibiotics around birth, as well as avoiding intubation of patients or promoting early removal of endotracheal tubes are among the most important preventive measures for ventilator-associated pneumonia. The use of probiotics and prebiotics to prevent infectious, allergic or metabolic complications in the short or long term constitutes a very important field of research in perinatal medicine.

The trillions of bacteria that live in and on our bodies make up the human microbiota, which is a very important part of keeping us healthy and protecting us from pathogenic infections. Dysbiosis is when there are changes in the composition and variety of the microbiota. This can upset the delicate balance between the host and its microbes, making the host more vulnerable to pathogens. Understanding the complicated link between microbiota and pathogens is important for coming up with effective ways to change microbiota and boost the body's defenses against infections. This study looks at how microbiota modulation affects the spread of pathogens and infections. It talks about how the makeup of microbiota affects how susceptible you are to pathogens. It shows how a healthy microbiota can protect you by making it hard for pathogens to grow and take over. The review also goes into detail about how the microbiota protects against pathogens, such as through competitive exclusion, the production of antimicrobial compounds, and the regulation of immune reactions. The study also looks at the idea of dysbiosis and how it is linked to pathogenic shifts. Disruptions in the microbiota can make it easier for pathogens to grow and make it harder for the host to fight off infections. It focuses on the need to recover microbial balance to improve the host's defenses and lower risks caused by pathogens. There is also talk about the use of probiotics, prebiotics, and fecal microbiota transplantation (FMT) as ways to change the microbiome. The goal of these interventions is to restore the diversity and function of microbes, improve the integrity of barriers, and boost the immune system's reaction to pathogens. The review shows how these methods could be used to change the microbiota and make it easier for the body to fight off infections. In conclusion, knowing how the microbiota and pathogens work together in a complicated way can help a lot when it comes to making specific interventions for microbiota modulation. Strategies that restore the balance of microbes and boost the host's defenses could stop pathogens from taking over and making people sick. More study needs to be done in this area to improve therapeutic approaches and use the microbiota to its fullest extent to fight infectious diseases.

Microbial communities inhabiting the human body play a crucial role in protecting the host against pathogens and inflammation. Disruptions to the microbial composition can lead to various health issues. Microbial transfer therapy (MTT) has emerged as a potential treatment option to address such issues. Fecal microbiota transplantation (FMT) is the most widely used form of MTT and has been successful in treating several diseases. Another form of MTT is vaginal microbiota transplantation (VMT), which involves transferring vaginal microbiota from a healthy female donor to a diseased patient's vaginal cavity with the goal of restoring normal vaginal microbial composition. However, VMT has not been extensively studied due to safety concerns and a lack of research. This paper explores the therapeutic mechanisms of VMT and discusses future perspectives. Further research is necessary to advance the clinical applications and techniques of VMT.

A growing body of evidences is showing that dysbiotic gut microbiota may correlate with a wide range of disorders; hence, the clinical use of microbiota maps and fecal microbiota transplantation (FMT) can be exploited in the clinic of some infectious diseases. Through direct or indirect ecological and functional competition, FMT may stimulate decolonization of pathogens or opportunistic pathogens, modulating immune response and colonic inflammation, and restoring intestinal homeostasis, with reduction of host damage. Herein, we discuss how diagnostic parasitology may contribute to design clinical metagenomics pipelines and FMT programs, especially in pediatric subjects. The consequences of a more specialized diagnostics in the context of gut microbiota communities may improve the clinical parasitology and extend its applications to the prevention and treatment of several communicable and even noncommunicable disorders.

The proximal part of the colon offers opportunities to prolong the absorption window following oral administration of a drug. In this work, we used computer simulations to understand how the hydrodynamics in the proximal colon might affect the release from dosage forms designed to target the colon. For this purpose, we developed and compared three different models: a completely-filled colon, a partially-filled colon and a partially-filled colon with a gaseous phase present (gas-liquid model).The highest velocities of the liquid were found in the completely-filled model, which also shows the best mixing profile, defined by the distribution of tracking particles over time. No significant differences with regard to the mixing and velocity profiles were found between the partially-filled model and the gas-liquid model. The fastest transit time of an undissolved tablet was found in the completely-filled model. The velocities of the liquid in the gas-liquid model are slightly higher along the colon than in the partially-filled model. The filling level has an impact on the exsisting shear forces and shear rates, which are decisive factors in the development of new drugs and formulations.

Recent studies have shown correlations between the microbiota's composition and various health conditions. Machine learning (ML) techniques are essential for analyzing complex biological data, particularly in microbiome research. ML methods help analyze large datasets to uncover microbiota patterns and understand how these patterns affect human health. This study introduces a novel approach combining statistical physics with the Monte Carlo (MC) methods to characterize bacterial species in the human microbiota. We assess the significance of bacterial species in different age groups by using notions of statistical distances to evaluate species prevalence and abundance across age groups and employing MC simulations based on statistical mechanics principles. Our findings show that the microbiota composition experiences a significant transition from early childhood to adulthood. Species such as Bifidobacterium breve and Veillonella parvula decrease with age, while others like Agathobaculum butyriciproducens and Eubacterium rectale increase. Additionally, low-prevalence species may hold significant importance in characterizing age groups. Finally, we propose an overall species ranking by integrating the methods proposed here in a multicriteria classification strategy. Our research provides a comprehensive tool for microbiota analysis using statistical notions, ML techniques, and MC simulations.

Currently, obesity is a critical global public health burden. Numerous studies have demonstrated the regulation of the pathogenesis of obesity and metabolic abnormalities by the gut microbiota and microbial factors; however, their involvement in the various degrees of obesity is not yet understood well. Previously, obesity has been shown to be associated with decreased levels of vitamin B12. Considering exclusive microbial production of vitamin B12, we hypothesised that a decrease in cobalamin levels in obese individuals may be at least partially caused by its depleted production in the intestinal tract by the commensal microbiota. In the present study, our aim was to estimate the abundance of enzymes and metabolic pathways for vitamin B12 synthesis in the gut microbiota of mouse models of alimentary and genetically determined obesity, to evaluate the contribution of the obesogenic microbiome to vitamin B12 synthesis in the gut. We have defined a significantly lower representation of enzymes and metabolic pathways for vitamin B12 biosynthesis in obese mice compared to non-obese mice, wherein enzyme depletion was more pronounced in lepr(-/-) (db/db) mice, which developed severe obesity. The representation of enzymes involved in cobalamin synthesis is strongly correlated with representation of several microbes in high-fat diet fed mice, whereas there were almost no correlations in db/db mice. Therefore, the degree of obesity and the composition of the correspondent microbiota are the main contributors to the representation of genes and pathways for cobalamin biosynthesis in the mouse gut.

The gut microbiota has recently been associated with susceptibility/resistance to malaria in animal models and humans, yet the impact of the gut microbiota on the risk of a malaria attack remains to be assessed. This study aims at assessing the influence of the gut microbiota on malaria attacks and Plasmodium parasitæmia in children living in a malaria-endemic area in Mali. Three hundred healthy children were included in a 16-months cohort study in Bandiagara. Their gut bacteria and fungi community structures were characterised via 16S and ITS metabarcoding from stool samples collected at inclusion. Clinician team monitored the occurrence of malaria attacks. Asymptomatic carriage of Plasmodium was assessed by qPCR. Over the 16-month period, 107 (36%) children experienced at least one occurrence of malaria attacks, and 82 (27%) at least one asymptomatic Plasmodium parasitæmia episode. A higher gut bacteria richness was independently associated with susceptibility to asymptomatic parasitæmia episodes and malaria attacks; while the Shannon H diversity and Chao-1 richness index of gut fungi community structure was relatively homogeneous in children who were and were not infected with P. falciparum. Using a linear discriminant effect size analysis of operational taxonomic units assigned to the species level, 17 bacteria, including Clostridiaceae, Eubacteriaceae, Senegalimassilia sp., Atopobiaceae and Lachnosipraceae, and seven fungi, including Dioszegia fristigensis, Ogataea polymorpha and Cutaneotrichosporon cyanovorans, were associated with susceptibility; whereas eight bacteria, including, Bifidobacterium spp., Weissela confusa and Peptostreptococcacea, and 3 fungi, Malassezia sp., Niesslia exosporoides, and Didymocrea leucaenae, were associated with resistance to malaria. Moreover, 15 bacteria, including Coproccus eutactus, Terrisporobacter petrolearius, Klebsiella pneumoniae and Ruminococcaceae, and 13 fungi, including Wallemia mellicola, were associated with susceptibility, whereas 19 bacteria, including Bifidobacterium spp., Bacteroides fragilis, Peptostreptococcacea, and Lactobacillus ruminis, and three fungi, including Cryptococcus neoformans, were associated with resistance to asymptomatic Plasmodium parasitæmia episodes. Further studies are needed to confirm these findings that point the way towards strategies aiming to reduce the risk of malaria by modulating gut microbiota components in at-risk populations.

The gut has been a focus of chronic disease research. The gut microbiota produces metabolites that act as signaling molecules and substrates, closely influencing host health. Indigestible oli-gosaccharides (NDOs), as a common dietary fiber, play an important role in regulating the structure and function of gut microbiota. Their mechanism of action is mainly attributed to their carbon source as specific probiotics, producing related metabolites, and regulating the gut mi-crobial community. However, due to the selective utilization of oligosaccharides, some factors such as the types and structures of oligosaccharides have different impacts on the composition of microbial populations and the production of metabolites in the colon ecosystem. This review systematically describes the key factors influencing the selective utilization of oligosaccharides in microorganisms and elaborates how oligosaccharides affect the host's immune system, inflam-mation levels and energy metabolism by regulating microbial diversity and metabolic function, which in turn will affect the onset and progress of chronic diseases, especially diabetes, obesity, depression and intestinal inflammatory diseases, constipation. In this review, we re-examine the interaction mechanisms between gut microbiota and its associated metabolites and diseases, and explore new strategies for promoting human health and combating chronic diseases through di-etary interventions.

Gut microbiota play critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance, which highlighted the potential of gut microbiota-targeted therapies on these diseases. There are various ways that can manipulate gut microbiota including probiotics, prebiotics, synbiotics, antibiotics and some active components from herbal medicines. In this review, we first reviewed the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies on NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.

Chickpea is an essential legume, a staple food in many cultures and contains nutrients with potential health benefits. The chickpea water (CPW) leached out after cooking is usually discarded, which may potentially have significant anti-cancer and other health beneficial properties. This study compared the in-vitro bioactivity of CPW with chickpea polyphenol extract (CPPE) to evaluate its impact on pathways of colorectal cancer progression and development. Morphological observation by APOPercentage, cell viability detection using a cytotoxic assay and cell migration-scratch assay points to measure rate of metastasis were employed. Overall antioxidant activity of CPW and CPPE were measured using ABTS and DPPH free-radical assays. At 50 µg/mL concentration and above, both CPW and CPPE extracts significantly reduce cell viability in HT-29 colon cancer cell lines (p < 0.05). Moreover, a quantitative analysis of the extent of apoptosis demonstrated that at 250 and 500 μg/mL concentrations, both extracts induced significant apoptosis compared to the untreated control. Meanwhile, the cell migration scratch area decreases by 34.42% and 15.27% when treated with CPW and CPPE, respectively. In summary, CPW demonstrated comparable in vitro anti-cancer properties and antioxidant activity in colorectal cancer cells to CPPE. Further, in vivo studies are warranted to evaluate the physiological bioactivity of CPW and CPPE in targeting pathways of cancer development and progression

Curcumin has attracted attention for its nontoxic chemopreventive effects; however, the specific pathways underlying its anticancer effects in colon cancer remain unclear. This study investigated the potential interplay between curcumin and integrin β1 in colon cancer. HCT116 and fibroblast cells were treated with curcumin, and cell proliferation was assessed using MTT assay and western blotting. We analyzed integrin β1 expression after curcumin treatment of HCT116 cells using western blotting and confocal microscopy. The roles of talin and rab25 in integrin β1 activation by curcumin were investigated using the same methods. Curcumin treatment significantly decreased the survival of HCT 116 cells but did not significantly affect the survival of fibroblast cells. Moreover, curcumin significantly increased integrin β1 expression in HCT 116 cells, which was primarily mediated by talin. In contrast, rab25 expression remained unchanged after curcumin treatment. Using rab25-specific siRNA knockdown experiments, we confirmed that curcumin increased integrin β1 expression even in the absence of rab25. Confocal microscopy revealed a dose-dependent increase in integrin β1 and talin expression, with consistent spatial distribution patterns in response to curcumin. This study highlights the clinical significance of curcumin as a selective anticancer agent in colon cancer by modulating integrin β1 expression through a talin-mediated pathway rather than through rab25.

Much evidence reveals an important link between gut microbiota and the heart. In particular, the gut microbiota plays a key role in the onset of cardiovascular (CV) disease, including heart failure (HF). In HF, splanchnic hypoperfusion causes intestinal ischemia resulting in the translocation of bacteria and their metabolites into the blood circulation. Among these, the most important is the Trimethylamine N-Oxide (TMAO), which is responsible through various mechanisms for pathological processes in different organs and tissues. In this review, we summarise the complex interaction between gut microbiota and CV disease, particularly with HF, and the possible strategies to influence its composition and function. Finally, we highlight the potential role of TMAO as a novel prognostic marker and new therapeutic target of HF.

Obesity in pregnancy induces metabolic syndrome, low-grade inflammation, altered endocrine factors, placental function, and the maternal gut microbiome. All these factors impact fetal growth and development, including brain development. The lipid metabolic transporters of the maternal-fetal-placental unit are dysregulated in obesity. Consequently, the transport of essential long-chain PUFAs for fetal brain development is disturbed. The mother’s gut microbiota is vital in maintaining postnatal energy homeostasis and maternal-fetal immune competence. Obesity during pregnancy changes the gut microbiota, affecting fetal brain development. Obesity and a high-fat diet in pregnancy can induce placental and intrauterine inflammation and thus influence the neurodevelopmental outcomes of the offspring. Several epidemiological studies observed an association between maternal obesity and adverse neurodevelopment. This review discusses the effects of maternal obesity and gut microbiota on fetal neurodevelopment outcomes. In addition, the possible mechanisms of the impacts of obesity and gut microbiota on fetal brain development are discussed.

Cannabis is one of the oldest cultivated crops in the history for food, fiber and drugs for thousands of years. Extension of cannabis genetic variation developed in a wide- ranging choice of varieties with various complementary phenotypes and secondary metabolites. Cannabis grow practices is very diverse, especially indoor cultivation factors, such as different lighting conditions, pot size, humidity, fertilizers. These growth factors influence a lot on the production of cannabinoids. For medical or pharmaceutical purposes, ratio of CBD or THC is very important. Plants traits and metabolic compounds are related to various conditions produced by microbes. Investigating this crosstalk between plants and microbes can play a vital role not only for stimulating the biosynthetic and signaling pathways of the host plants for the production of agronomically or pharmaceutically essential metabolic compounds but also against pathogens. This study emphasis on decoding the crosstalk between cannabis and associated microbes in the belowground environmental niches that would unravel the complexity of stabilizing cannabinoid production.

Gut bacteria play an important role in several metabolic processes and human diseases, such as obesity and its co-morbidities, like fatty liver disease, insulin resistance/diabetes and cardiovascular events. Among several factors, dietary patterns, probiotics, prebiotics, synbiotics, antimicrobials and non-dietary factors, such as stress, age, exercise and climatic conditions, can dramatically impact the human gut microbiota diversity and equilibrium. However, the effect of minor food constituents, including food additives and trace contaminants, on human gut microbiota has received less attention. Consequently, the present review aimed to provide an objective perspective of the current knowledge regarding the impacts of minor food constituents on human gut microbiota and consequently, on human health.

(1) Background: Heat stress detrimentally restricted the economic in dairy farming production, therefore, this study was designed to investigate how automatic spraying method on alleviating heat stress on cows. (2) Methods: A total of 1208 multiparous dairy cows were randomly allocated into 6 barns, three barns were equipped with automatic sprinklers (SP), each barn was considered as a replicate. The other three barns were considered as control treatments (CON). Each barn was considered as a replicate. (3) Results: body temperature and milk somatic cell count were significantly decreased, while DMI, milk yield, and milk fat content significantly increased with spraying treatment. ICR was improved from 30% to 35%. Rumen fermentation was enhanced by the increased levels of total VFA, acetate, propionate, and butyrate with the spraying treatment. Rumen microbiota results showed at the phylum level, rumen Fibrobacters abundance significantly increased by the spraying treatment. At the genus level, Eubacterium, Shuttleworthia, Saccharofermentans, Lachnospira, Pseudobutyrivibrio, Selenomonas, and Succinivibrio abundance were significantly increased, while Ruminococcaceae and Rikenellaceae abundance were significantly decreased in the rumen with spraying treatment. (4) Conclusion: this study demonstrated automatic spraying modulated the rumen microbiota composition and fermentation function, and effectively meliorated side-effects of heat stress on dairy cows.

This study addresses the urgent need for sustainable protein sources in aquaculture due to the depletion of marine resources and rising costs. Animal protein sources, particularly poultry by-product meal (PBM) and insect exuviae meal, are investigated as viable alternatives to fishmeal (FM). Research confirms the successful replacement of FM with a combination of PBM and insect exuviae meal (up to 50%) in the diet of European seabass without compromising growth, feed conversion, gut health and liver fat content. In particular, growth performance was robust with both PBM formulations, with the 25% PBM diet showing better results. Histological examinations showed good gut and liver health, contradicting the concerns of previous studies. The study emphasizes the importance of holistic analyzes that go beyond growth parameters and include histomorphological investigations. The results show that PBM in combination with insect/exuviae meal is well tolerated by seabass, which is consistent with literature reports of mitigating negative effects on gut health. A detailed analysis of the microbiota revealed a decrease in the Firmicutes/Proteobacteria ratio due to an increase in potentially pathogenic bacteria. However, the formulation containing insect exuviae partially counteracted this effect by preserving the beneficial Lactobacillus and promoting the synthesis of short-chain fatty acids (SCFA), particularly butyrate. Chitin-rich components from insect exuviae were associated with improved gut health, which was supported by increased production of SCFA, which are known for their anti-inflammatory properties. The study concludes that a combination of PBM and insect/exuviae meal can replace up to 50% of FM in the diet of seabass, supporting sustainable aquaculture practices. Despite some changes in the microbiota, the negative effects are mitigated by the addition of insect exuviae, highlighting their potential as a prebiotic to increase fish productivity and contribute to a circular economy in aquaculture.

Uremic toxins are the compounds that emerge in the blood when kidney excretory function is impaired. The cumulative detrimental effect of uremic toxins results in numerous health problems and eventually death during acute or chronic uremia, especially in end-stage renal disease. More than 100 different solutes rise during uremia; however, the exact origin for most of them is still discussable. There are 3 main sources for such compounds: exogenous ones are consumed with food, whereas endogenous are produced by host metabolism or by symbiotic microbiota metabolism. In this article, we identified uremic toxins presumably of gut microbiota origin. We analyzed various databases to get information on enzymatic reactions in bacteria and human organism potentially yielded uremic toxins and to determine what toxins could be synthetized in bacteria residing in human gut. We selected biochemical pathways resulting in uremic toxins synthesis related to specific bacterial strains, and revealed links between toxin concentration in uremia and the proportion of different bacteria species, which can synthesize it. Moreover, we defined the relative abundance of human toxin-generating enzymes as well as the possibility of a particular toxin synthesis by the human metabolism. Finally, we analyzed which bacteria are potentially producing the biggest number of uremic toxins as well as which bacteria are decomposing them. Our study presents a bioinformatics-based approach for both elucidation of the origin of uremic toxins and search of the most likely human microbiome producers of toxins that can be targeted and used for the therapy of adverse consequences of uremia.

5-Pentadecylresorcinol (C15) is a natural alkylresorcinol that has been shown to protect against complications caused by imbalanced nutrition. Although the exact mechanisms of beneficial activity of C15 are not known, we assume that the protective effects of C15 on metabolic health are mediated by their modulatory influence on the composition of the intestinal microbiota and functional activity. Cobamides and vitamin B12 are believed to be crucial modulators of mammalian gut ecosystems. We proposed that C15 may influence the representation of enzymes and pathways for vitamin B12 synthesis in the gut microbiome, providing compositional and functional changes in the microbial community. High-throughput metagenome sequencing of the contents of the small and large intestines of C57Bl6 mice fed a regular or high-fat diet with or without C15 supplementation was performed followed by reconstruction of the metabolic activity of the microbiota to clarify the role of C15 in vitamin B12 synthesis by the gut microbiota. It has been established that C15 significantly increases the representation of the cobalamin salvage pathway and enzymes in the microbiome of the large intestine of mice fed a high-fat diet. The genera Clostridium, AF12, and [Ruminococcus] had shown the highest number of correlations with enzymes for B12 synthesis and were negatively associated with the representation of probiotic bacteria. Therefore, the beneficial effect of C15 on the gut microbiota community can be achieved by modulating B12 synthesis that, in turn, serves as one of the key regulators of gut microbiota ecology.

Emerging evidence suggests that the human vermiform appendix is not a vestigial organ, but rather an immunological organ of biological relevance. It is hypothesised that the appendix acts as a bacterial ‘safe house’ for commensal gut bacteria and facilitates re-inoculation of the colon after disruption through the release of biofilms. To date, no studies have attempted to explore this potential mechanistic function of the appendix. We conducted a pre-post intervention study in adults (n=59) exploring reestablishment of the gut microbiota in those with and without an appendix after colonic disruption via bowel preparation and colonoscopy. Gut microbiota composition was measured one week before and one month after bowel preparation and colonoscopy using 16S rRNA sequencing. We observed between group differences in gut microbiota composition between those with (n=45) and without (n=13) an appendix at baseline. These differences were no longer evident one-month post-procedure, suggesting that this procedure may have ‘reset’ any potential appendix-related differences between groups. Both groups experienced reductions in gut microbiota richness and shifts in beta diversity post-procedure, with greater changes in those without an appendix, and there were five bacterial genera whose re-establishment post-procedure appeared to be moderated by appendicectomy status. This small experimental study provides preliminary evidence of a potential differential reestablishment of the gut microbiota after disruption in those with and without an appendix, warranting further investigation into the potential role of the appendix as a microbial safe house.

There is a growing interest in the endocannabinoid system and the gut microbiota. Both areas have been suggested to play a role in endometriosis, however this is yet to be studied comprehensively. The purpose of this narrative review is to identify the gaps in endometriosis research in the context of these two areas. It underscores the limited knowledge regarding the involvement of the endocannabinoid system and gut microbiota in endometriosis. Further research in these areas is essential to unlock the therapeutic potential of cannabis and enhance the understanding of endometriosis pathogenesis.

Abstract: Early life gut microbiota have been increasingly recognized as major contributors to short and/or long-term human health and diseases. Numerous studies have demonstrated that human gut microbial colonization begins at birth but continues to develop a succession of taxonomic abundances for two to three years until the gut microbiota reaches adult-like diversity and proportions. Several factors, including gestational age (GA), delivery mode, birth weight, feeding types, antibiotic exposure, maternal microbiome and diet influence the diversity, abundance and function of the early life gut microbiota. Gut microbial life is essential for assisting with the digestion of food substances to release nutrients, exerting control over pathogens, stimulating or modulating the immune system and influencing many systems such as the liver, brain, and endocrine system. Microbial metabolites play multiple roles in these interactions. Furthermore, studies provide evidence supporting that imbalances of the gut microbiota in early life, referred to as dysbiosis, are associated with specific childhood or adult disease outcomes, such as asthma, atopic dermatitis, diabetes, allergic diseases, obesity, cardiovascular diseases (CVD) and neurological disorders. These findings support that the human gut microbiota may play a fundamental role in the risk of acquiring diseases that may be programmed during the early life stage. In fact, it is critical to explore the role of the human gut microbiota in early life. In this review, we summarize the general understanding of the colonization and development of the gut microbiota in early life, highlighting the recent findings regarding the relationship between the gut microbiota composition and their metabolites, and immune functions, which could significantly influence long-term health and disease. We then review known pathophysiological interactions of the early gut microbiome with a number of well characterized diseases and pose potential etiological mechanisms.

Egyptian mongoose (Herpestes ichneumon) is a medium-size carnivore that in Europe is restricted to Iberia. The bio-ecology of this species remains to be elucidated in several dimensions, including gut microbiota that is nowadays recognized as a fundamental component of mammals. In this work, we investigated the gut microbiota of this herpestid by single-molecule real-time sequencing of twenty paired male (n=10) and female (n=10) intestinal samples. This culture-independent approach enabled microbial profiling based on 16S rDNA and investigation of taxonomical and functional features. The core gut microbiome of the adult subpopulation was dominated by Firmicutes, Fusobacteria, Actinobacteria, and Proteobacteria. Eight genera were uniquely found in adults and five in non-adults. When comparing gut bacterial communities across sex, four genera were exclusive of females and six uniquely found in males. Despite these compositional distinctions, alpha- and beta-diversity analyses showed no statistically significant differences across sex or between adult and non-adult specimens. However, males presented a significantly higher abundance of amino acid and citrate cycle metabolic pathways, compared to the significant overrepresentation in females of galactose’ metabolic pathways. Adults showed a significantly higher abundance of cationic antimicrobial peptide resistance pathways, while non-adults bared a significant overrepresentation of two-component systems associated with antibiotic synthesis, flagellin production and chemotaxis control. This study adds new insights into mongoose bio-ecology palette, highlighting taxonomical and functional microbiome dissimilarities across sex and age classes, possibly related to primary production resources and life-history traits that impact on behavior, diet and gut ecosystem.

Background: Colorectal cancer (CRC) is prevalent globally, constituting 11.9% of cases in Mexico. Lymph node metastases are established prognostic indicators, with extracapsular lymph node extension (ENE) playing a crucial role in modifying prognosis. While ENE is associated with adverse factors, certain aspects, like lymph node conglomerates, are underexplored. Matted nodes, clusters of lymph nodes infiltrated by cancer cells, are recognized as an independent prognostic factor in other cancers. This study investigates the prognostic implications of lymph node conglomerates, particularly matted nodes, in colon cancer. Methods: A retrospective analy-sis of 502 colon cancer cases (2005–2018) identified 255 with lymph node metastasis. Cases were categorized into two groups: 1) lymph node metastasis alone (n=208), and 2) lymph node metas-tasis with matted nodes (n=47). A comparative survival analysis was performed. Results: Of the 255 patients, 38% had lymph node metastasis. Patients with matted nodes (18.4%) showed an association with higher pN stage and lymphovascular invasion. The 5-year survival rate for pa-tients with matted nodes was 47.7%, compared to 60% without; however, this association demonstrated only a statistical tendency. Multivariate analysis identified clinical stage and ad-juvant chemotherapy use as independent factors contributing to survival. Conclusion: This study underscores matted nodes as potential prognostic indicators in colon cancer, emphasizing their association with higher pN stage and reduced survival. Further research is essential for validat-ing these findings and integrating matted nodes into the broader context of colorectal cancer management.

Human colon carcinomas, including HCT116 cells, often exhibit high basal autophagic flux under nutrient deprivation or hypoxic conditions. Mitochondrial ROS (mROS) is known as a “molecular switch”’ for regulating the autophagic pathway, which is critical for directing cancer cell survival or death. In early tumorigenesis, autophagy plays important roles in maintaining cellular homeostasis and contributes to tumor growth. However, the relationships between mROS and the autophagic capacities of HCT116 cells are poorly understood. Ubiquinol cytochrome c reductase binding protein (UQCRB) has been reported as a biomarker of colorectal cancer, but its role in tumor growth has not been clarified. Here, we showed that UQCRB was overexpressed in HCT116 cells compared to CCD18co cells, a normal colon fibroblast cell line. Pharmacological inhibition of UQCRB reduced mROS levels, autophagic flux, and the growth of HCT116 tumors in a xenograft mouse model. We further investigated mutant UQCRB-overexpressing cell lines to identify functional links in UQCRB-mROS-autophagy. Notably, an increasing level of mROS caused by UQCRB overexpression released Ca2+ by activation of lysosomal TRPML1 channels. This activation induced transcription factor EB nuclear translocation and lysosome biogenesis, leading to autophagy flux. Collectively, our study showed that increasing levels of mROS caused by overexpression of UQCRB in human colon carcinoma HCT116 cells could be linked to autophagy for cell survival.

Huntington’s disease (HD) is a rare but progressive and devastating neurodegenerative disease characterized by involuntary movements, cognitive decline, executive dysfunction, and neuropsychiatric conditions such as anxiety and depression. It follows an autosomal dominant inheritance pattern. Thus, a child who has a parent with the mutated huntingtin (mHTT) gene has a 50% chance of developing the disease. Since HTT protein is involved in many critical cellular processes including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, and autophagy, its aberrant aggregates lead to disruption of numerous cellular pathways and neurodegeneration. Essential heavy metals are vital at low concentrations, however, at higher concentrations, can exacerbate HD by disrupting the glial-neuronal communication, and/or causing dysbiosis (disturbance in the gut microbiota, GM), both of which can lead to neuroinflammation and further neurodegeneration. Here, we discuss in detail the interactions of iron, manganese and copper with glial-neuron communication and GM and indicate how this knowledge may pave the way for development of a new generation of disease-modifying therapies in HD.

Evidence is emerging on the role of maternal diet, gut microbiota, and other lifestyle factors in establishing lifelong health and disease, which are determined by trans-generationally inherited epigenetic modifications. Understanding epigenetic mechanisms may help identify novel biomarkers for pregnancy-related exposure, burden, or disease risk. Such biomarkers are essential for developing tools for the early detection of risk factors and exposure levels. It is necessary to establish the exposure threshold to the fetus due to nutrient deficiencies or other environmental factors that can lead to clinically relevant epigenetic changes that modulate disease risks. This narrative review summarizes the latest updates on the roles of maternal nutrients (n-3 fatty acids, polyphenols, vitamins) and gut microbiota on the placental epigenome and its impacts on fetal brain development.

Recent advancements in gut microbiome research have highlighted the complex interplay between gut microbiota and various physiological and pathological processes, showing that gut microbiota plays a vital role in human health and disease. Imbalances in the gut microbiota, known as dysbiosis, have been associated with a range of health conditions, including gastrointestinal disorders, metabolic diseases, etc. In response to these findings, probiotics, prebiotics, synbiotics, and postbiotics have emerged as a promising therapeutic strategy to modulate gut microbiota composition and functionality. This review paper explores the latest research on how gut microbiota impacts host physiology, immune responses, and overall well-being. Furthermore, the paper delves into the therapeutic potential of probiotics, postbiotics, prebiotics, and synbiotics in therapeutic applications and curing various diseases. The paper also addresses the challenges and opportunities in the field, highlighting the need for personalized approaches to probiotic therapy and the importance of considering factors such as strain specificity, dosing, and safety.Overall, this review aims to provide a comprehensive overview of the evolving landscape of gut microbiota and probiotics, prebiotics, synbiotics, and postbiotics as novel therapeutic agents. It underscores the potential of harnessing the gut microbiome to improve health, prevent diseases, and complement traditional medical interventions. As research in this field continues to expand, a deeper understanding of the gut microbiota and probiotics, prebiotics, synbiotics, and postbiotics promises new avenues for preventive and therapeutic healthcare strategies.

Carbapenems-resistant enterobacteria are considered multidrug-resistant, making the control of their nosocomial infections a major challenge in healthcare settings. It is important to know the incubation site and source of the spread of these strains, especially in neonatal intensive care units (NICU). Colonization of the colon of preterm neonates per se by multidrug-resistant bacterial strains could be the source of dissemination of these multidrug-resistant strains and their site of incubation. In this study, colonization of the colon of preterm neonates with enterobacteria and their multidrug-resistant strains was investigated. The presence of enterobacteria in the stool of preterm neonates was investigated on EMB (eosin-methylene blue) agar, followed by morphological and biochemical characterization and phylogenetic analysis of the 16S rRNA-encoding gene sequences. Antibiotic susceptibility of all isolated strains was tested using VITEK 2 technology. All cases examined at two weeks of age and older showed bacterial colonization of the colon. Klebsiella pneumoniae colonized the colon in 56.2% of the preterm neonates and Klebsiella quasipneumoniae was found in 6.3%, corresponding to 62.5% in total. The colonizing Klebsiella pneumoniae was multidrug-resistant in 2 of 9 cases. One strain of Klebsiella pneumoniae was resistant to carbapenems and another showed intermediate resistance to these antibiotics. These Klebsiella pneumoniae strains showed resistance to most of the other antibiotics tested. Some cases contained more than one genus, with Escherichia coli found in 50% of cases in preterm neonates. In contrast to Klebsiella pneumoniae, none of the E. coli strains colonizing the colon of preterm neonates in this study showed resistance to carbapenems. The results of this study suggest that Klebsiella pneumoniae and its carbapenems multidrug-resistant strains are well marked in preterm neonates colonizing their colon, which is the incubation site and source of such multidrug-resistant bacterial strains in NICU. This study highlights the importance of careful management of preterm neonates in the NICU and possible contamination with multidrug-resistant Klebsiella pneumoniae incubated in their colon. Further studies would be of interest to avoid the possibility of fecal-oral transmission and infection by these multidrug-resistant bacteria and their treatment in the colon, where their incubation site is located.