Oral bacterial composition associated with lung function and lung inflammation in a community-based Norwegian population.

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 Clostridiales, Achromobacter, Moraxella, Flavitalea and Helicobacter were significantly different among those with low FEV1 (< lower limit of normal (LLN)) as compared to normal FEV1 i.e. ≥ LLN. Twenty-three genera differed in abundance between among those with low FVC < LLN as compared to normal FEV1 ≥ LLN. The abundance of 27 genera from phyla Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria and Sacchribacteria differed significantly between elevated FeNO levels (≥ 50 ppb) compared to FeNO ≤ 25 ppb. CONCLUSION: Oral bacterial composition was significantly different for those with low FEV or FVC as compared to those with normal lung function equal to or higher than LLN. Differential bacterial composition was also observed for elevated FeNO levels.

Association of oral bacteria with oral hygiene habits and self-reported gingival bleeding.

AIM: To 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 METHODS: We 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. RESULTS: Gingival bacterial diversity increased with increasing frequency of self-reported gingival bleeding, with higher Shannon diversity index for "always" ß = 0.51 and "often" ß = 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 denticola, and Fretibacterium spp., but lower abundance of bacteria within the gram-positive phyla Firmicutes and Actinobacteria. Flossing and rinsing with mouthwash twice daily were associated with higher total abundance of bacteria in the Proteobacteria phylum but with lower bacterial diversity compared to those who never flossed or never used mouthwash. CONCLUSIONS: A high frequency of self-reported gingival bleeding was associated with higher bacterial diversity than found in participants reporting no gingival bleeding and with higher total abundance of known periodontal pathogens such as Porphyromonas spp., Treponema spp., and Bacteroides spp.

Exposure to environmental phenols and parabens, and relation to body mass index, eczema and respiratory outcomes in the Norwegian RHINESSA study.

BACKGROUND: Many phenols and parabens are applied in cosmetics, pharmaceuticals and food, to prevent growth of bacteria and fungi. Whether these chemicals affect inflammatory diseases like allergies and overweight is largely unexplored. We aimed to assess the associations of use of personal care products with urine biomarkers levels of phenols and paraben exposure, and whether urine levels (reflecting body burden of this chemical exposures) are associated with eczema, rhinitis, asthma, specific IgE and body mass index. METHODS: Demographics, clinical variables, and self-report of personal care products use along with urine samples were collected concurrently from 496 adults (48% females, median age: 28 years) and 90 adolescents (10-17 years of age) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan (TCS), triclocarban (TCC), parabens and benzophenone-3, bisphenols and dichlorophenols (DCP) were quantified by mass spectrometry. RESULTS: Detection of the urine biomarkers varied according to chemical type and demographics. TCC was detected in 5% of adults and in 45% of adolescents, while propyl (PPB) and methyl (MPB) parabens were detected in 95% of adults and in 94% (PPB) and 99% (MPB) of adolescents. Women had higher median urine concentrations of phenolic chemicals and reported a higher frequency of use of personal care products than men. Urine concentration of MPB increased in a dose-dependent manner with increased frequency of use of several cosmetic products. Overall, urinary biomarker levels of parabens were lower in those with current eczema. The biomarker concentrations of bisphenol S was higher in participants with positive specific IgE and females with current asthma, but did not differ by eczema or rhinitis status. MPB, ethylparaben (EPB), 2,4-DCP and TCS were inversely related to BMI in adults; interaction by gender were not significant. CONCLUSIONS: Reported frequency of use of personal care products correlated very well with urine biomarker levels of paraben and phenols. Several chemicals were inversley related to BMI, and lower levels of parabens was observed for participants with current eczema. There is a need for further studies of health effects of chemicals from personal care products, in particular in longitudinally designed studies.

Bloating in Irritable Bowel Syndrome Is Associated with Symptoms Severity, Psychological Factors, and Comorbidities.

BACKGROUND: Bloating is one of the most bothersome symptoms of irritable bowel syndrome (IBS), but its association with other symptoms is not well described. AIMS: We investigated the association between symptoms of abdominal bloating, other IBS symptoms, psychological distress, and comorbid pain conditions. METHODS: We conducted a cross-sectional study on a large cohort of IBS patients with and without symptoms of abdominal bloating and healthy controls. Subjects were assessed for IBS and its subtypes, pain severity, symptoms severity, psychological disturbances, comorbidities, and dietary restrictions of three fluid groups. RESULTS: A total of 484 subjects were investigated. Compared with IBS - B, IBS + B subjects had higher rates of constipation (30% vs. 15%, p = 0.191) and lower rates of diarrhea, (70% vs. 85%, p = 0.191) although these were not statistically significant. Bloating severity correlated with IBS symptoms severity (r = 0.397, p = 0.000), pain severity (r = 0.364, p = 0.000), and both anxiety and somatization scores (r = 0.167, p = 0.015 and r = 0.219, p = 0.001, respectively). Prevalence of fibromyalgia and depression and somatization scores was significantly higher in IBS with bloating than in IBS without bloating. IBS patients with bloating reported more dietary restriction of three fluid groups to control their symptoms compared with healthy controls and IBS patients without bloating. CONCLUSIONS: Abdominal bloating in IBS is associated with increased symptoms and pain severity, somatization, depression, fibromyalgia, and altered dietary fluids composition. Recognizing and addressing these factors in the diagnosis and management of patients with IBS may improve clinical outcome.

Testing in Microbiome-Profiling Studies with MiRKAT, the Microbiome Regression-Based Kernel Association Test.

High-throughput sequencing technology has enabled population-based studies of the role of the human microbiome in disease etiology and exposure response. Distance-based analysis is a popular strategy for evaluating 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 selecting the best distance and extending the methods to alternative 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 machine regression framework. MiRKAT allows for easy covariate adjustment and extension to alternative outcomes while non-parametrically modeling the microbiome through a kernel that incorporates phylogenetic distance. It uses a variance-component score statistic to test for the association with analytical p value calculation. The model also allows simultaneous examination of multiple distances, alleviating the problem of choosing the best distance. Our simulations demonstrated that MiRKAT provides correctly controlled type I error and adequate power in detecting overall association. "Optimal" MiRKAT, which considers multiple candidate distances, is robust in that it suffers from little power loss in comparison to when the best distance is used and can achieve tremendous power gain in comparison to when a poor distance is chosen. Finally, we applied MiRKAT to real microbiome datasets to show that microbial communities are associated with smoking and with fecal protease levels after confounders are controlled for.

Practice Differences in the Diagnosis and Management of Eosinophilic Esophagitis Among Adult and Pediatric Gastroenterologists in Israel.

OBJECTIVES: Eosinophilic esophagitis (EoE) guidelines call for similar practices in adults and children with EoE. We compared the diagnostic and management practices of gastroenterologists treating adult and pediatric patients suspected of having, or diagnosed with, EoE. METHODS: A 19-question multiple-choice questionnaire was given to gastroenterologists treating either adults or children. Questions explored 4 areas of interest: physician demographics, diagnosis and tissue sampling practices, management, and the need for societal publications on EoE. RESULTS: Completed questionnaires were returned by 85/180 adult and 30/40 pediatric gastroenterologists (PGs). Compared to PGs, adult gastroenterologists (AGs) took esophageal biopsies significantly less frequently in the following scenarios: endoscopy without esophageal symptoms or macroscopic endoscopic findings (10% vs 57%; P < 0.001), dysphagia without macroscopic findings (83% vs 100%; P = 0.019), and gastroesophageal reflux symptoms with distal esophageal erythema (44% vs 100%; P < 0.001). Significantly fewer AGs reported taking gastric and duodenal biopsies when EoE was suspected (29% vs 90%; P < 0.001). AGs more often followed patients clinically (30% vs 0%; P < 0.001) rather than endoscopically, and were far less inclined to implement elimination diets compared to PGs (23% vs 68%; P < 0.001). CONCLUSIONS: Significant disparities exist between gastroenterologists treating adult and pediatric patients with EoE. These findings may impact rates of diagnosis, appropriate treatment, monitoring, long-term outcomes, and may affect negatively transition from pediatric to adult care.

Fecal and Mucosa-Associated Intestinal Microbiota in Patients with Diarrhea-Predominant Irritable Bowel Syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) has been associated with changes in the intestinal microbiota. Only a few studies have explored differences in the mucosa-associated microbiota between IBS patients and healthy controls (HC). AIMS: To characterize and compare the microbiota in mucosal and fecal samples from carefully selected patients with IBS-D and HC. METHODS: The cohort was composed of 23 diarrhea-predominant IBS (IBS-D) patients and 24 HC. Fresh stool samples were collected from participants prior to the collection of colonic mucosal samples from an unprepped bowel. After DNA extraction, 16S rRNA genes were sequenced by 454 pyrosequencing and analyzed using the QIIME pipeline. RESULTS: The fecal microbiota (luminal niche) of IBS-D patients was found to have reduced enteric richness compared to HC (P < 0.05), whereas no differences were observed between the two groups within the mucosal microbiota. Within the luminal niche, the relative proportions of Faecalibacterium genus were found to be lower in IBS-D than in HC and the Dorea genus was higher in IBS-D. None of the taxa proportions were significantly different in IBS-D patients versus HC using an FDR of ≤ 0.1 when analyzing samples that appeared in > 25% samples of either niche. CONCLUSION: Fecal and mucosal microbiota of IBS-D patients and HC are very similar and are not sufficient to explain the reported altered physiology and symptomatology of IBS-D. Future studies should investigate intestinal microbiome-dependent functional activity in addition to the fecal and mucosal-associated microbial composition.

Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Evaluate the Benefit of the Probiotic Bifidobacterium infantis 35624 in Non-Patients With Symptoms of Abdominal Discomfort and Bloating.

OBJECTIVES: 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 (109 c.f.u. per day) for the relief of abdominal discomfort and bloating in a non-patient population. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Molecular characterization of the intestinal microbiota in patients with and without abdominal bloating.

Recent studies have demonstrated differences in the intestinal microbiota between patients with irritable bowel syndrome (IBS) and healthy controls (HC), suggesting a role for the intestinal microbiota in the pathogenesis of IBS. Alterations in the microbiota have also been implicated in the pathogenesis of abdominal bloating, a commonly reported symptom in IBS. We investigated the relationship between the intestinal microbiota, abdominal bloating, and altered bowel patterns in a cohort of patients with IBS and HC. The 16S rRNA gene from fresh fecal samples was amplified and pyrosequenced by using Roche-454 Titanium chemistry. A Core Measurable Microbiome (CMM) was generated for Operational Taxonomic Unit (OTU) detected in >75% of all samples and compositional features of CMM were compared between groups by Linear Discriminant Analysis (LDA). IBS differentiated from HC by LDA using continuous variation in the species/OTUs or the CMM genera. When subcategorized based on bloating symptoms and bowel characteristics, the same subjects were also well differentiated from one another and from HC. ANOVA analysis showed quantitative species/OTU differences between the subgroups including IBS with and without bloating, and subtypes based on bowel characteristics. The clear LDA differentiation and the significant microbial taxa differences between the groups imply a significant association of the microbiota with bloating symptoms and bowel characteristics in IBS. These changes in the microbiota may serve as a biomarker for IBS and its clinical subtypes and suggest a role for the intestinal microbiota in the pathogenesis of the main symptoms of the disorder.

High-sensitive C-Reactive Protein as a Marker for Inflammation in Irritable Bowel Syndrome.

BACKGROUND: Recent studies demonstrated low-grade inflammation in patients with irritable bowel syndrome (IBS). However, these studies have been relatively small and do not enable examination of this factor in different subtypes of IBS and the possibility of confounding effects of comorbidities that may be associated with inflammatory responses. GOALS: To investigate the association between high-sensitive C-reactive protein (hs-CRP) and the diagnosis of IBS, IBS subtypes, symptoms' severity, and IBS-associated comorbidities. STUDY: This cross-sectional study uses data from a large matched case-control study of IBS subjects and healthy controls (HC). hs-CRP levels were measured in all subjects. IBS diagnosis was determined by Rome III criteria, negative screening blood tests, and normal colonoscopy. Subjects were evaluated for IBS severity and associated pain and psychological comorbidities. RESULTS: A total of 242 IBS patients and 244 HC were studied. Median hs-CRP levels in the IBS group were significantly higher than in HC (1.80; interquartile range, 0.7 to 4.04 mg/L vs. 1.20, interquartile range, 0.5 to 2.97 mg/L respectively, P<0.006). Levels were highest in IBS-D patients with greater disease severity. Hs-CRP levels mildly correlated with symptoms severity (r=0.169, P=0.009); this correlation was stronger for the IBS-D patients (r=0.27, P=0.006). IBS was a significant independent predictor (P=0.025) for higher hs-CRP levels, whereas other pain and psychological comorbidities were not. CONCLUSIONS: Given these observations of cross-sectional differences in hs-CRP between IBS subtypes and severity, independent of pain and comorbidities, more research is needed to explore a possible role of low-grade inflammation in the pathogenesis and/or clinical presentation of IBS.

Altered Colonic Bacterial Fermentation as a Potential Pathophysiological Factor in Irritable Bowel Syndrome.

OBJECTIVES: Dysbiosis leading to abnormal intestinal fermentation has been suggested as a possible etiological mechanism in irritable bowel syndrome (IBS). We aimed to investigate the location and magnitude of altered intestinal bacterial fermentation in IBS and its clinical subtypes. METHODS: IBS patients who satisfied the Rome III criteria (114) and 33 healthy controls (HC) were investigated. Intestinal fermentation was assessed using two surrogate measures: intestinal intraluminal pH and fecal short-chain fatty acids (SCFAs). Intraluminal pH and intestinal transit times were measured in the small and large bowel using a wireless motility capsule (SmartPill) in 47 IBS and 10 HC. Fecal SCFAs including acetate, propionate, butyrate, and lactate were analyzed by capillary gas chromatography in all enrolled subjects. Correlations between intestinal pH, fecal SCFAs, intestinal transit time, and IBS symptom scores were analyzed. RESULTS: Colonic intraluminal pH levels were significantly lower in IBS patients compared with HC (total colonic pH, 6.8 for IBS vs. 7.3 for HC, P=0.042). There were no differences in total and segmental pH levels in the small bowel between IBS patients and HC (6.8 vs. 6.8, P=not significant). The intraluminal colonic pH differences were consistent in all IBS subtypes. Total SCFA level was significantly lower in C-IBS patients than in D-IBS and M-IBS patients and HC. The total SCFA level in all IBS subjects was similar with that of HC. Colonic pH levels correlated positively with colon transit time (CTT) and IBS symptoms severity. Total fecal SCFAs levels correlated negatively with CTT and positively with stool frequency. CONCLUSIONS: Colonic intraluminal pH is decreased, suggesting higher colonic fermentation, in IBS patients compared with HC. Fecal SCFAs are not a sensitive marker to estimate intraluminal bacterial fermentation.

Randomized, double-blind, placebo-controlled study of synbiotic yogurt effect on the health of children.

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.

The Intestinal Microbiota and Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is the most prevalent and the best studied functional gastrointestinal disorder. The etiology and the pathogenesis of IBS are still not clear; however, recent studies have implicated a role for alterations in the intestinal microbiota (dysbiosis) in the pathophysiology of the disorder. Epidemiological observations have demonstrated that the development of IBS symptoms is often preceded by a disruption of the individual's normal intestinal microbiota, and microbiological studies have demonstrated compositional differences in the intestinal microbiota between patients with IBS patients and healthy controls. In addition, animal studies and a few recent human clinical studies have demonstrated that compositional changes in the intestinal microbiota in IBS are associated with relevant abnormal gastrointestinal and brain-gut axis functions that are often observed in patients with IBS. This article discusses points of interest from the current research on the microbiota-gut-brain interactions in IBS and highlights the relevance of the emerging data to our understanding of the disorder and the clinical implications for patients' care.

Luminal cysteine-proteases degrade colonic tight junction structure and are responsible for abdominal pain in constipation-predominant IBS.

OBJECTIVES: Luminal serine-proteases lead to increased colonic paracellular permeability and visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Other proteases, namely cysteine-proteases (CPs), increase airway permeability by digesting epithelial tight junction proteins. In this study, we focused on constipation-predominant IBS (IBS-C) and we aimed to (i) evaluate CP levels in two cohorts of IBS patients, (ii) test if IBS-C fecal supernatant (FSN) affects permeability, and visceral sensitivity after repeated administrations in mice, and (iii) evaluate occludin expression in IBS-C colonic biopsies. METHODS: Fecal CP activity was determined using selective substrate and inhibitor (E64). The effect of papain, as positive control, and IBS-C FSN administrations were evaluated on colonic paracellular permeability and mucosal occludin levels in mice and T84 monolayers. Occludin protein levels were evaluated in IBS-C colonic biopsies. Sensitivity to colorectal distension (CRD) was measured after repeated administrations of IBS-C FSN. RESULTS: We found in a subset of IBS-C patients an enhanced fecal CP activity, in comparison with healthy controls and IBS-D patients. CP activity levels positively correlated with disease severity and abdominal pain scoring. This association was confirmed by receiver operating characteristic curve analysis. In mice, repeated application of IBS-C FSN into colon triggered increased permeability, linked to the enzymatic degradation of occludin, and was associated with enhanced visceral sensitivity to CRD. Finally, occludin levels were found decreased in colonic biopsies from IBS-C patients, and IBS-C FSNs were able to degrade recombinant human occludin in vitro. All these effects were abolished by preincubation of IBS-C FSN with a CP inhibitor, E64. CONCLUSIONS: These data suggest that luminal CPs may represent a new factor contributing to the genesis of symptoms in IBS.

Early life exposures as risk factors for pediatric eosinophilic esophagitis.

OBJECTIVES: Few etiologic studies of eosinophilic esophagitis (EoE) have been conducted. Early life exposures have been shown to predispose to other allergic disease, but their role has not been assessed in EoE. The present study sought to explore early life exposures as possible risk factors for developing EoE in the pediatric population. METHODS: This was a 2-phase case-control study conducted at the University of North Carolina. The first phase consisted of survey development for early life exposures via cognitive interview. In the second phase, a telephone-based questionnaire was administered to cases with EoE (n = 31) and 2 sets of controls, patients with gastroesophageal reflux disease, and siblings of nonsyndromic cleft lip/palate patients (n = 26 in each). Different controls were explored to identify controls reflective of the source population of the cases. Siblings of cleft lip/palate patients were identified as the more suitable control population. Odds ratios were calculated to evaluate the association between early life exposures and the development of pediatric EoE. RESULTS: Early life exposures were associated with increased odds of developing pediatric-onset EoE. Antibiotic use in infancy was associated with 6 times the odds of having EoE (95% confidence interval 1.7-20.8). Cesarean delivery, preterm birth, and formula-only or mixed (infant formula and breast milk) feeding also have trends toward increased odds for developing EoE. CONCLUSIONS: A number of early life exposures may be associated with the development of EoE. These are potentially modifiable risk factors that if confirmed would have implications for improved understanding of EoE pathogenesis and disease prevention.

Genetic Variants in Carbohydrate Digestive Enzyme and Transport Genes Associated with Risk of Irritable Bowel Syndrome.

Irritable Bowel Syndrome (IBS) is characterized by abdominal pain and alterations in bowel pattern, such as constipation (IBS-C), diarrhea (IBS-D), or mixed (IBS-M). Since malabsorption of ingested carbohydrates (CHO) can cause abdominal symptoms that closely mimic those of IBS, identifying genetic mutations in CHO digestive enzymes associated with IBS symptoms is critical to ascertain IBS pathophysiology. Through candidate gene association studies, we identify several common variants in TREH, SI, SLC5A1 and SLC2A5 that are associated with IBS symptoms. By investigating rare recessive Mendelian or oligogenic inheritance patterns, we identify case-exclusive rare deleterious variation in known disease genes (SI, LCT, ALDOB, and SLC5A1) as well as candidate disease genes (MGAM and SLC5A2), providing potential evidence of monogenic or oligogenic inheritance in a subset of IBS cases. Finally, our data highlight that moderate to severe IBS-associated gastrointestinal symptoms are often observed in IBS cases carrying one or more of deleterious rare variants.

Exposure to Antibacterial Chemicals Is Associated With Altered Composition of Oral Microbiome.

Antimicrobial chemicals are used as preservatives in cosmetics, pharmaceuticals, and food to prevent the growth of bacteria and fungi in the products. Unintentional exposure in humans to such chemicals is well documented, but whether they also interfere with human oral microbiome composition is largely unexplored. In this study, we explored whether the oral bacterial composition is affected by exposure to antibacterial and environmental chemicals. Gingival fluid, urine, and interview data were collected from 477 adults (18-47 years) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan, triclocarban, parabens, benzophenone-3, bisphenols, and 2,4- and 2,5-dichlorophenols (DCPs) were quantified (by mass spectrometry). Microbiome analysis was based on 16S amplicon sequencing. Diversity and differential abundance analyses were performed to identify how microbial communities may change when comparing groups of different chemical exposure. We identified that high urine levels (>75th percentile) of propyl parabens were associated with a lower abundance of bacteria genera TM7 [G-3], Helicobacter, Megasphaera, Mitsuokella, Tannerella, Propionibacteriaceae [G-2], and Dermabacter, as compared with low propylparaben levels (<25th percentile). High exposure to ethylparaben was associated with a higher abundance of Paracoccus. High urine levels of bisphenol A were associated with a lower abundance of Streptococcus and exposure to another environmental chemical, 2,4-DCP, was associated with a lower abundance of Treponema, Fretibacterium, and Bacteroidales [G-2]. High exposure to antibacterial and environmental chemicals was associated with an altered composition of gingiva bacteria; mostly commensal bacteria in the oral cavity. Our results highlight a need for a better understanding of how antimicrobial chemical exposure influences the human microbiome.

Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome.

Alterations in the intestinal microbiota have been suggested as an etiological factor in the pathogenesis of irritable bowel syndrome (IBS). This study used a molecular fingerprinting technique to compare the composition and biodiversity of the microbiota within fecal and mucosal niches between patients with diarrhea-predominant IBS (D-IBS) and healthy controls. Terminal-restriction fragment (T-RF) length polymorphism (T-RFLP) fingerprinting of the bacterial 16S rRNA gene was used to perform microbial community composition analyses on fecal and mucosal samples from patients with D-IBS (n = 16) and healthy controls (n = 21). Molecular fingerprinting of the microbiota from fecal and colonic mucosal samples revealed differences in the contribution of T-RFs to the microbiota between D-IBS patients and healthy controls. Further analysis revealed a significantly lower (1.2-fold) biodiversity of microbes within fecal samples from D-IBS patients than healthy controls (P = 0.008). No difference in biodiversity in mucosal samples was detected between D-IBS patients and healthy controls. Multivariate analysis of T-RFLP profiles demonstrated distinct microbial communities between luminal and mucosal niches in all samples. Our findings of compositional differences in the luminal- and mucosal-associated microbiota between D-IBS patients and healthy controls and diminished microbial biodiversity in D-IBS fecal samples further support the hypothesis that alterations in the intestinal microbiota may have an etiological role in the pathogenesis of D-IBS and suggest that luminal and mucosal niches need to be investigated.

The rationale and clinical effectiveness of probiotics in irritable bowel syndrome.

The pathophysiology of irritable bowel syndrome (IBS) is still unknown. However, several lines of epidemiological, physiological, and clinical data suggest a role for intestinal bacteria in the pathogenesis of the disorder. Recent microbiology studies demonstrated differences in the composition of the intestinal microbiota between patients with IBS and healthy individuals. In addition, physiological studies have shown that manipulation of the intestinal microbiota by antibiotics, prebiotics, or probiotics can affect intestinal functions (eg, motility and sensation) relevant in the pathogenesis of IBS. Several randomized control trials comparing the effects of probiotics versus placebo in IBS have been published. Despite considerable differences in study design, dosing regimens, probiotic species used, and reported clinical end points, the current data indicate improving IBS symptoms and reducing the risk of persistent IBS symptoms. The data on the use of probiotics in children with IBS is more limited but is also suggestive for beneficial effects. The inconsistencies between the studies underline the need to look at each probiotic product separately for specific conditions, symptoms, and patient populations. This review article discusses the rationale for targeting the intestinal microbiota in patient with IBS and provides an overview and a critical evaluation of the currently available clinical data on the use of probiotics in the treatment of patients with IBS.