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OBJECTIVE To assess the effects of daily consumption of a synbiotic yogurt drink on the health, growth, and quality of life of healthy children 12-48 months of age in out-of-home child care. STUDY DESIGN Healthy children attending child... more
OBJECTIVE To assess the effects of daily consumption of a synbiotic yogurt drink on the health, growth, and quality of life of healthy children 12-48 months of age in out-of-home child care. STUDY DESIGN Healthy children attending child care centers were enrolled in a prospective, double-blind, placebo-controlled clinical trial. The intervention was a yogurt drink containing Streptococcus thermophilus, Lactobacillus bulgaricus, and Bifidobacterium animalis subspecies lactis (BB-12) (5 × 10(9) cfu/100 mL serving), and 1 g of inulin (synbiotic group) vs a similar nonsynbiotic-containing acidified milk drink (placebo group) once daily for 16 weeks. The end points were days of diarrhea, fever, vomiting, symptoms of upper respiratory tract infection, use of antibiotics, physician visits, child care absenteeism, parental work absenteeism, and quality of life (PedsQL 4.0; Mapi Research Trust, Lyon, France). RESULTS Compared with placebo (n = 73), children receiving synbiotic (n = 76) had significantly fewer days of reported fever (1.85 vs 1.95, P < .05), significant improvement in social functioning (P < .035; pre-to-end intervention), and school functioning (P < .045; pre-to-mid intervention). More days with ≥ 3 loose/watery stools were reported in the synbiotic group (P < .05). CONCLUSIONS Daily supplementation of children's diet with yogurt containing probiotic bacteria BB-12 and inulin significantly reduced days of fever and improved social and school functioning. The increased frequency of bowel movements may be explained by an accelerating effect of BB-12 and inulin on intestinal transit. Further research on the possible benefits of synbiotics on children's health is advised. TRIAL REGISTRATION ClinicalTrials.gov: NCT00653705.
Background: Previous studies indicated that lung health might be affected by both antibacterial chemicals and poor oral health. Aims and objective: Describe association between oral microbiome and paraben exposure, asthma and lung... more
Background: Previous studies indicated that lung health might be affected by both antibacterial chemicals and poor oral health. Aims and objective: Describe association between oral microbiome and paraben exposure, asthma and lung function. Methods: Interview data, lung function, gingival fluid and urine were collected from 288 adults (48% females, median age: 28 yrs) from the RHINESSA study in Bergen, Norway. Differential abundance in the gingival microbiome (Illumina sequencing) across dose groups (quartiles) for urine biomarkers of paraben exposure was evaluated using the Analysis of composition of microbiomes (ANCOM) methodology with 5% FDR, adjusting for gender and asthma status. Association between microbial diversity and lung function was assessed by linear regression with adjustment for height, weight, age, smoking, and asthma medication. Results: Propyl- and methyl-parabens were detected in 94% subjects, with 62 times higher concentration in women than men. With increasing exposure to parabens, Enterobacter spp in the gingival fluid decreased in a dose-response manner, whereas Fretibacterium spp increased. FEV 1 and FVC increased with increasing microbiome diversity in women; FEV 1 with b (95% CI) =0.13 (0.02, 0.24) and FVC with b=0.15 (95% CI: 0.01, 0.28) per unit increase in Shannon index. No association was seen for men. Conclusions: Lung function increased with increasing oral microbial diversity in women only. Paraben exposure was associated with bacteria linked to poor oral health (Fretibacterium), independent of gender and asthma status (including asthma medication). Exposure to antibacterial chemicals may modify the association between oral microbiome and lung health.
The intestinal microbiota is a functional organ with a variety of important metabolic, trophic, immunologic, and digestive activities. Current data suggest that alterations in the intestinal microbiota may be related to disease... more
The intestinal microbiota is a functional organ with a variety of important metabolic, trophic, immunologic, and digestive activities. Current data suggest that alterations in the intestinal microbiota may be related to disease conditions. Manipulation of the intestinal microbiota such as with probiotics, prebiotics, and synbiotics may be beneficial in preventing and treating certain disease conditions. This article provides an overview of the evidence gathered through randomized clinical trials, reviews, and meta-analyses on probiotics and prebiotics in commonly studied conditions in the pediatric population. It concludes with current recommendations for their use, noting safety and gaps in clinical evidence.
Background: Poor oral health, indicated as a risk factor for other disease outcomes, such as cardiovascular and respiratory disease, may be associated with specific microbial compositions. We aimed...
Alterations in the intestinal microbiota have been implicated in the pathogenesis of irritable bowel syndrome (IBS). Recent studies using advanced molecular biology techniques have demonstratedmicrobiota compositional differences between... more
Alterations in the intestinal microbiota have been implicated in the pathogenesis of irritable bowel syndrome (IBS). Recent studies using advanced molecular biology techniques have demonstratedmicrobiota compositional differences between IBS patients and healthy controls (HC). Many of these studies, however, are confounded by the fact that the study populations comprise a mixed group of patients with IBS or a specific subtype of IBS. Thus, there is a need for systematic comparison of microbiota composition between subjects with clinicallyrelevant subtypes of IBS. Aim: To investigate the differences in composition of the intestinal microbiota between clinically-relevant, well-defined subgroups of patients with IBS and HC using deep pyrosequencing of the 16S rRNA gene. Methods: DNA was isolated from fecal samples from 60 IBS patients (Rome III: C-IBS, D-IBS, M-IBS; n=20 per group) and 20 HC. The V1-V2 variable regions of the 16S rRNA gene were amplified using bar-coded fusion primers and pyrosequenced using Roche-454 Titanium chemistry. Sequences were processed through the Multi-CLASSIFIER algorithm for taxonomic assignment. Classified reads were assigned to a species/OTU-level status using BLAST pipeline. Unclassified readswere clustered into OTUs at 97% using CD-Hit. A Core Measurable Microbiome (CMM) was generated for OTUs detected in ≥75% of all samples. Compositional features of CMM were compared using Linear Discriminant Analysis (LDA). Quantitative differences in species/OTUs and taxonomic groups were tested by ANOVA with the Tukey correction for multiple testing. Results: Subjects with IBS differentiated from HC by LDA using continuous variation in the species/OTUs or the CMM genera as variables. When further subcategorized based on bowel characteristics, the same subjects were also well-differentiated from one another and from HC. ANOVA analysis showed quantitative species/OTUs differences between the study subgroups: I. a significant increase in members of the Actinobacteria phyla (in particular the genus Collinsiella) in the C-IBS subgroup compared to all other groups, II. a significant decrease in members of Firmicutes phyla ( Oscillibacter, Anaerovorax, Incertae sedis XIII, Streptococcus and Eubacteriaceae) in D-IBS and M-IBS compared to HC and C-IBS, and III. a significant lower levels of Lactobacillus in HC compared to C-IBS and D-IBS. Conclusion: We demonstrated clear differences in the intestinal microbiota between patients with clinically-relevant subtypes of IBS. While differences in many individual taxa were identified, there was little difference in the relative abundances of major taxonomic groups (e.g., ratio of Bacteriodetes;Firmicutes:Proteobacteria). Our results provide a rationale for further investigation of the causality and the role of these microbiota compositional alterations in the pathogenesis of IBS.
Bifidobacterium infantis 35624 is a probiotic that is used often in patients with irritable bowel syndrome (IBS). Non-patients with bowel symptoms may differ from patients with IBS in the impact of their bowel symptoms on illness... more
Bifidobacterium infantis 35624 is a probiotic that is used often in patients with irritable bowel syndrome (IBS). Non-patients with bowel symptoms may differ from patients with IBS in the impact of their bowel symptoms on illness severity, healthcare and treatment seeking behavior. The aim of this study is to assess the efficacy of B. infantis 35624 (10 c.f.u. per day) for the relief of abdominal discomfort and bloating in a non-patient population. A double-blind, randomized, placebo-controlled, parallel study with a 2-week placebo run-in phase followed by a 4-week intervention phase was conducted at ten clinical centers (USA). Subjects were recruited from the general population by advertisement. The study randomized 302 subjects who experienced abdominal discomfort and bloating ≥2-times per week for at least three months but have not seen a physician or received prescribed medication for their symptoms in the past 12 months. Subjects were assessed for pre- to post-intervention changes in symptom severity (on a 6-point Likert scale; 0=none, 5=very severe) and frequency (symptoms-free days). A total of 275 subjects (mean age 42 years, 79% female, 74% Caucasian) provided evaluable data. Overall mean severity scores at baseline were 2.4 for abdominal discomfort and 2.5 for bloating with no significant differences between the placebo and probiotic groups. Both groups showed significant (P<0.05) improvement in abdominal discomfort and bloating scores over the 4-week intervention period. Mean severity symptom scores at the end of intervention showed no significant differences between the probiotic and the placebo groups in either abdominal discomfort or bloating (P>0.3). The frequency of abdominal bloating-free days was greater in the B. infantis 35624 group compared to the placebo group (P<0.05). Both regimens were well tolerated. Unlike previous clinical studies in patients with IBS, B. infantis 35624 did not show a significant improvement in the mean severity of symptoms of abdominal discomfort and bloating in a non-patient population. This may be explained by the high placebo effect and the lower impact of functional bowel symptoms in the non-patient population.
Gut colonization by beneficial bacteria in early life is necessary for establishing the gut mucosal barrier, maturation of the immune system and preventing infections with enteric pathogens. Mode of delivery, prematurity, breastfeeding,... more
Gut colonization by beneficial bacteria in early life is necessary for establishing the gut mucosal barrier, maturation of the immune system and preventing infections with enteric pathogens. Mode of delivery, prematurity, breastfeeding, and use of antibiotics are some of many factors that have been described to influence early life colonization. Dysbiosis, the absence of normal colonization, is associated with many disease conditions. Pre- and probiotics are commonly used as supplementation in infant formula, such as prebiotic oligosaccharides for stimulation of Bifidobacterium growth aiming to mimic the high levels of these commensal bacteria in the gut of breastfed infants. Studies suggest that probiotic supplementation may be beneficial in prevention and management of disease (e.g., reducing the risk of necrotizing enterocolitis in preterm infants and treatment of acute gastroenteritis in children). Although these studies show promising beneficial effects, the long-term risks or health benefits of pre- and probiotic supplementation are not clear.
Increased activity of fecal proteases has been reported in patients with irritable bowel syndrome (IBS). Animal studies demonstrated that fecal proteases induce physiological alterations in intestinal motility, sensation and permeability,... more
Increased activity of fecal proteases has been reported in patients with irritable bowel syndrome (IBS). Animal studies demonstrated that fecal proteases induce physiological alterations in intestinal motility, sensation and permeability, similar to those found in patients with IBS. Fecal cysteine-protease has been suggested to have a role in the pathogenesis of C-IBS. However, fecal cysteine-protease has not been investigated in other subtypes of IBS and its relationship with IBS symptoms and intestinal physiology is unknown. Aims: To measure and compare the level of fecal cysteine-protease activity (FCPA) between patients with IBS, subtypes of IBS, and healthy controls and to investigate the relationship between FCPA, abdominal pain, IBS severity and gastrointestinal transit. Methods: We studied a total of 60 patients who met the Rome III criteria for IBS (C-IBS, n=14; D-IBS, n=28; MIBS, n=18) and 34 healthy controls. FCPA was measured in homogenized fecal samples of all subjects using an enzymatic-based method with specific substrates and inhibitors, and expressed as Δfluo/mg protein. Abdominal pain was assessed using a 0-10 scale and IBS severity scores was assessed by IBS-Symptom Severity Scale. Wireless Motility Capsule (SmartPillTM) was used to measure small bowel (SBTT), colonic (CTT), and whole gut (WGTT) transit times. Comparisons of FCPA between the groups of interest were done using student t-tests. Pearson correlation analysis was used to assess the association between FCPA and clinical and physiological variables. Results: Compared to HC, subjects with IBS, and all subtypes of IBS, had significantly higher levels of FCPA (HC: 128.0±334.4; all IBS: 595.9±853.1, p=0.03; D-IBS: 447.4±635.2, p=0.014; M-IBS: 749.9±748.5, p<0.0001; CIBS: 694.8±1281.2, p=0.02 respectively). Subjects with C-IBS had significantly higher FCPA levels than D-IBS (p<0.0001). FCPA levels showed a significant positive correlation with abdominal pain (r=0.37, p=0.006) and a trend of a positive correlation with IBS symptom severity (r=0.24, p=0.08). No correlation was found between FCPA levels and the transit time variables of interest. Demographic characteristics were similar between the groups. Conclusions: We provide evidence for significant differences in FCPA between patients with IBS, subtypes of IBS and healthy controls. FCPA is strongly correlated with abdominal pain, a hallmark symptom of IBS. These findings suggest a role for luminal cysteine protease in the pathogenesis of IBS.
Colonization of the human gut microbiome begins in utero and continues through infancy and into childhood. Microbiota of the human gut share a symbiotic relationship with the human host and early life dysbiosis may contribute to acute and... more
Colonization of the human gut microbiome begins in utero and continues through infancy and into childhood. Microbiota of the human gut share a symbiotic relationship with the human host and early life dysbiosis may contribute to acute and distal health effects. Numerous factors in early life may contribute to the establishment of the microbiome and to dysbiosis, including maternal, intrapartum, and postnatal factors. Elucidating the contribution of these factors to health and disease, as mediated by the establishment of the gut microbiome, may offer not only insights into disease pathogenesis, but also opportunities for disease prevention and mitigation through manipulation of the gut microbiome.
Background The oral cavity is the gateway to the bacteria community in the lung. Disruption of the symbiotic balance of the oral microbiota has been associated with respiratory diseases. However, little is known about the relationship... more
Background The oral cavity is the gateway to the bacteria community in the lung. Disruption of the symbiotic balance of the oral microbiota has been associated with respiratory diseases. However, little is known about the relationship between oral bacteria and respiratory outcomes in the general population. We aimed to describe the associations between oral bacteria, lung function, and lung inflammation in a community-based population. Methods Oral (gingival) samples were collected concurrently with spirometry tests in 477 adults (47% males, median age 28 years) from the RHINESSA study in Bergen, Norway. Bacterial DNA from the 16S rRNA gene from gingival fluid were sequenced by Illumina®MiSeq. Lung function was measured using spirometry and measurement of fractional exhaled nitric oxide (FeNO) were performed to examine airway inflammation. Differential abundance analysis was performed using ANCOM-BC, adjusting for weight, education, and smoking. Results The abundance of the genera C...
AimTo describe associations of gingival bacterial composition and diversity with self‐reported gingival bleeding and oral hygiene habits in a Norwegian regional‐based population.Materials and MethodsWe examined the microbiome composition... more
AimTo describe associations of gingival bacterial composition and diversity with self‐reported gingival bleeding and oral hygiene habits in a Norwegian regional‐based population.Materials and MethodsWe examined the microbiome composition of the gingival fluid (16S amplicon sequencing) in 484 adult participants (47% females; median age 28 years) in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) study in Bergen, Norway. We explored bacterial diversity and abundance differences by the community periodontal index score, self‐reported frequency of gingival bleeding, and oral hygiene habits.ResultsGingival bacterial diversity increased with increasing frequency of self‐reported gingival bleeding, with higher Shannon diversity index for “always” β = 0.51 and “often” β = 0.75 (p < .001) compared to “never” gingival bleeding. Frequent gingival bleeding was associated with higher abundance of several bacteria such as Porphyromonas endodontalis, Treponema denticol...
The pathophysiology of irritable bowel syndrome (IBS) is believed to involve alterations in the brain-gut axis; however, the etiological triggers and mechanisms by which these changes lead to symptoms of IBS remain poorly understood.... more
The pathophysiology of irritable bowel syndrome (IBS) is believed to involve alterations in the brain-gut axis; however, the etiological triggers and mechanisms by which these changes lead to symptoms of IBS remain poorly understood. Although IBS is often considered a condition without an identified “organic” etiology, emerging evidence suggests that alterations in the gastrointestinal microbiota and altered immune function may play a role in the pathogenesis of the disorder. These recent data suggest a plausible model in which changes in the intestinal microbiota and activation of the enteric immune system may impinge upon the brain-gut axis, causing the alterations in gastrointestinal function and the clinical symptoms observed in patients with IBS. This review summarizes the current evidence for altered intestinal microbiota and immune function in IBS. It discusses the potential etiological role of these factors, suggests an updated conceptual model for the pathogenesis of the di...
Additional file 3.
The 60 and 120 minute calculations were similar. The overall variability for pH 30 minutes from each landmark is in Table 1. Conclusion: This is the first study to perform tandem gut transit and pH assessments in healthy subjects. Our... more
The 60 and 120 minute calculations were similar. The overall variability for pH 30 minutes from each landmark is in Table 1. Conclusion: This is the first study to perform tandem gut transit and pH assessments in healthy subjects. Our preliminary results demonstrate that within 24 hours, there is little overall variability in transit time and pH in the GI tract of healthy volunteers as measured by the SmartPill device. Completion of additional subjects will clarify these findings and provide essential information for the reliability of future SmartPill studies. Funding: The SmartPill company provided no funding support for this investigator initiated study.
High-throughput sequencing technology has enabled population based studies into the role of the human microbiome in disease etiology and expo-sure response. Distance based analysis is a popular strategy to evaluate the overall association... more
High-throughput sequencing technology has enabled population based studies into the role of the human microbiome in disease etiology and expo-sure response. Distance based analysis is a popular strategy to evaluate the overall association between microbiome diversity and outcome, wherein the phylogenetic distance between individuals ’ microbiome profiles is computed and tested for association via permutation. Despite their practical popularity, distance based approaches suffer from important challenges, especially in the difficulty in selecting the best distance and in extending the methods to al-ternative outcomes, such as survival outcomes. We propose the microbiome regression-based kernel association test (MiRKAT), which directly regresses the outcome on the microbiome profiles via the semi-parametric kernel ma-chine regression framework. MiRKAT allows for easy covariate adjustment
Novel optical probes allow quantification of bile salt hydrolase activity in bacteria, clinical fecal samples, mice, and humans.

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