Microbiota-Short Chain Fatty Acid Relationships and Microbial Substrate Preferences Vary Across the Spectrum of Irritable Bowel Syndrome (IBS).

Objective: Identifying microbial targets in irritable bowel syndrome (IBS) is challenged by dynamic microbiota-metabolite-host interactions. We aimed to assess microbial features associated with short chain fatty acids (SCFA) and determine if features were related to IBS symptoms, subtypes, and endophenotypes. Design: We performed an observational study of stool microbial metagenomes, stool SCFA, and IBS traits (stool form, stool bile acids, and colonic transit) in patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and healthy controls. We analyzed associations of microbiome composition with stool SCFA to identify microbe-SCFA relationships that were shared and distinct across groups. We compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by stool characteristics. In IBS-D, we compared stool microbiomes of patients with and without bile acid malabsorption (BAM). Results: Overall stool microbiome composition and abundances of individual taxa differed between groups. Increased abundances of several bacterial species were observed in IBS-D including Dorea sp. CAG:317.. Microbes-SCFA relationships varied across groups after accounting for transit and bile acids. Significant microbe-SCFA were common in IBS-D and several SCFA-producing species were inversely correlated with SCFA. Among participants selected by stool form characteristics, functional profiling demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D with BAM. Conclusion: Microbe-SCFA associations differ across IBS subtypes and traits. Altered substrate preferences offer insights into functional microbiome traits and could be used as novel microbial IBS biomarkers. KEY MESSAGES: What is already known on this topic: The intestinal microbiota and its metabolites (e.g., short chain fatty acids [SCFA]) modulate irritable bowel syndrome (IBS) pathophysiology. What this study adds: We studied microbe-SCFA associations across IBS subtypes and endophenotypes to demonstrate (1) the intestinal microbiome plays distinct roles across IBS subtypes, (2) microbial substrate preferences vary between IBS subtypes and influences stool form, and (3) microbe-SCFA patterns may reveal key taxa that underlie shared and distinct microbial mechanisms across the IBS spectrum. How this study might affect research, practice or policy: Findings demonstrate that structural and functional features of the intestinal microbiome may represent unbiased microbial biomarkers for clinical and mechanistic IBS subtypes. Further study of these putative microbial targets as well as their interactions with diet- and host-specific traits should be pursued to develop individualized microbiome-based approached to IBS management.

Self-Reported Gluten Intolerance Is Prevalent, but Not All Gluten-Containing Foods Are Equal.

BACKGROUND: Celiac disease prevalence approaches 1%; more suffer from non-celiac gluten sensitivity. AIMS: Our goal was to estimate the prevalence of gluten intolerance. METHODS: We invited US adults (18-80 years) via Amazon's mechanical Turk to complete an online survey. Gluten intolerance was defined as self-reported intolerance to wheat, barley, rye, flour, or pasta. Those with celiac disease were not excluded. RESULTS: We collected 2133 responses. Rate of gluten intolerance was 5.1% (95% CI 4.2-6.1%). Each food had different rates: wheat 4.8%, flour 1.2%, pasta 0.9%, barley 0.8%, and rye 0.8%. Among 108 adults reporting any gluten intolerance, 62.0% selected only wheat, 10.2% selected all gluten-containing grains excluding pasta and flour, and 5.6% selected all gluten-containing products. Overall intolerance to any food was 24.8% (95% CI 23.0-26.6%). Wheat was second only to lactose. CONCLUSIONS: Self-reported intolerance to wheat, but not all gluten-containing foods, is common. Findings may suggest poor knowledge of gluten-containing foods or that self-perceived non-celiac gluten sensitivity is prevalent.

Relationships of Intestinal Lactase and the Small Intestinal Microbiome with Symptoms of Lactose Intolerance and Intake in Adults.

BACKGROUND: Approximately two-thirds of adults are genetically predisposed to decreased lactase activity after weaning, putting them at risk of lactose intolerance. However, symptoms are a poor marker of lactose maldigestion. AIMS: We assessed association between self-reported lactose intolerance and intestinal lactase, lactose intake, and the small intestinal microbiome. METHODS: Patients 18-75 years presenting for upper endoscopy were recruited prospectively. Observational study participants completed a lactose intolerance symptom questionnaire and reported lactose intake. Post-bulbar biopsies were obtained to measure lactase activity and assess the small intestinal mucosal microbiome. We compared intestinal lactase between patients with and without lactose intolerance. We assessed associations between lactose intolerance symptoms and lactase and lactose intake. We examined associations of small bowel microbial composition with self-reported lactose intolerance and symptoms. RESULTS: Among 34 patients, 23 (68%) reported lactose intolerance. Those with lactose intolerance had higher total symptom scores, more frequent bowel urgency, and more bowel movements after consuming dairy. The proportion of individuals with abnormal lactase activity did not differ by lactose intolerance status. Median lactase levels were correlated with total lactose intolerance symptom scores (p = 0.038) and frequency of bowel urgency (p = 0.012). Daily lactose intake did not differ between groups. In 19 patients, we observed significant associations of small intestinal microbiome beta diversity with stool consistency after consuming dairy (p = 0.03). CONCLUSIONS: Intestinal lactase is associated with lactose intolerance symptoms and bowel urgency in adults but does not distinguish the clinical phenotype entirely. Studying other contributing factors (microbiota, diet) may further clarify the pathophysiology of lactose intolerance.

Associations of Habitual Dietary Intake With Fecal Short-Chain Fatty Acids and Bowel Functions in Irritable Bowel Syndrome.

BACKGROUND GOALS: Diet may contribute to symptoms of irritable bowel syndrome (IBS) and luminal production of putative IBS biomarkers including short-chain fatty acids (SCFAs). Study aims were to to assess relationships of habitual fiber or starch intake with fecal SCFAs in patients with IBS and healthy volunteers (HVs). STUDY: In 18 HVs and 30 patients with IBS (13 constipation-predominant [IBS-C] and 17 diarrhea-predominant [IBS-D]), habitual diet using a food frequency questionnaire; bowel functions using a validated bowel diary; and fecal SCFAs by HPLC-mass spectrometry were assessed. Associations of fiber and starch with SCFAs were analyzed using Spearman (rs) and Pearson (R) correlations. Relationships between other dietary endpoints, SCFAs, and bowel functions were explored. RESULTS: Habitual fiber or starch intakes were not significantly correlated with SCFAs or bowel functions in all participants or HVs nor with SCFAs in IBS. Starch was negatively correlated (R=-0.53; P=0.04) with complete evacuation in IBS-D. Fiber (rs=0.65; P=0.02) and starch (rs=0.56; P=0.05) were correlated with ease of passage in IBS-C. Stool form, frequency, and ease of passage were positively correlated with total SCFAs (all P<0.05), acetate (all P<0.01), propionate (all P<0.05), and butyrate (form P=0.01; ease of passage P=0.05) among all participants, but not in IBS. Complete evacuation was negatively correlated with propionate (R=-0.34; P=0.04) in all participants. Total (P=0.04) and individual SCFAs (all P<0.05) were positively correlated with stool form in HVs. CONCLUSIONS: Habitual fiber and starch intake does not influence fecal SCFAs but may influence bowel functions in IBS. Fecal SCFAs correlate with bowel functions among all participants including HVs.

Early adverse life events and post-traumatic stress disorder in patients with constipation and suspected disordered defecation.

BACKGROUND: Early adverse life events (EALs) and post-traumatic stress disorder (PTSD) are associated with irritable bowel syndrome (IBS). Disordered defecation (DD) presents with symptoms of IBS or functional constipation (FC) and is associated with psychological distress. However, the role of trauma and stress in chronic constipation is poorly defined. We aimed to examine EALS, PTSD, and psychological symptoms in patients with constipation and suspected DD. METHODS: We conducted a survey study among adults with constipation who completed anorectal manometry (ARM) and balloon expulsion testing (BET). Data were collected on socio-demographics, EALs, PTSD, bowel symptoms, quality of life, and anxiety and depression. We performed comparisons between individuals with normal versus abnormal ARM or BET, subgroup analysis by detailed ARM and BET findings, and latent class analysis using individual EAL domains. KEY RESULTS: Among 712 eligible patients, 69 completed the study. EALs and provisional PTSD were present in 75.4% and 27.5%, respectively; rates did not differ between those with normal versus abnormal ARM or BET. Normal testing was associated with higher rates of specific EAL domains (emotional abuse and mental illness), higher depression scores, and poorer mental component scores in both primary and subgroup comparisons (all p < 0.05). Normal testing was associated with a lower likelihood of high-EAL latent class (p = 0.01) membership. Presence of IBS or FC did not influence associations. CONCLUSIONS & INFERENCES: Early adverse life events and PTSD are prevalent in patients with constipation and suspected DD. Those with normal ARM and BET have higher rates of prior emotional abuse and poorer mental health.

Associations of Food Intolerance with Irritable Bowel Syndrome, Psychological Symptoms, and Quality of Life.

BACKGROUND & AIMS: The impact of different types of food intolerance on gastrointestinal symptoms and quality of life (QOL) is poorly understood. We aimed to investigate associations of food intolerance and type of intolerance with irritable bowel syndrome (IBS), health-related QOL, and psychological symptoms. METHODS: We conducted an observational study of United States-based adults through an online survey. Demographics, culprit foods, symptoms, medical evaluation, Rome IV criteria for IBS, health-related QOL (Short-Form Health Survey 12), and anxiety and depression scores (Hospital Anxiety and Depression Scale) were collected in participants with self-reported food intolerance (lactose, non-lactose food, lactose plus food intolerance), and controls with no intolerance. Univariable associations of group with study endpoints were analyzed with the Kruskal-Wallis and Pearson χ2 or Fisher exact test. Multivariable comparisons were analyzed by logistic and linear regression. RESULTS: A total of 197 patients with (59 lactose, 61 non-lactose food, 77 lactose plus food intolerance) and 273 patients without intolerance participated. Lactose, wheat, and eggs were the most common food triggers. Gas (54.2%), abdominal pain (40.2%), and diarrhea (37.3%) were frequently reported symptoms of food intolerance. Reactions caused 57.8% to eliminate the food. Rates of IBS, abnormal anxiety scores, and abnormal depression scores were highest in lactose plus food intolerance; Short-Form Health Survey 12 scores were lowest in lactose plus food intolerance. Multivariable analyses revealed all intolerance subgroups were more likely to have IBS than controls. CONCLUSIONS: Food intolerance is associated with IBS, anxiety, depression, and decreased health-related QOL and frequently leads to food elimination. Adults with lactose and lactose plus food intolerance have higher rates of IBS, increased psychological symptoms, and poorer QOL.

High prevalence of food intolerances among US internet users.

OBJECTIVE: Food intolerances are commonly reported and are predicted to have gastrointestinal health implications. We aimed to quantify the prevalence of food intolerances among US adults and identify culprit foods through a brief web-based survey. DESIGN: We invited participation in an online cross-sectional survey involving a single questionnaire. Data were summarised using percentages or medians and interquartile range. Participant characteristics by self-reported food intolerance were compared using the Wilcoxon rank sum test and Pearson's χ2 test. Adjusted analyses were performed using multivariable logistic regression. SETTING: The survey was internet-based via Amazon's mechanical Turk, a crowdsourcing website for the completion of requester directed tasks. PARTICIPANTS: Adults who were US-based internet users were invited at ages 18-80. RESULTS: We collected 2133 survey responses (ages 18-79 years). The rate of food intolerance was 24·8 % (95 % CI 23·0, 26·6) in US adults. Younger (P < 0·01), female (P = 0·05) and Asian, African American or multiple race individuals (P < 0·01) predominated. Lactose intolerance was most common. Frequency of a non-lactose food intolerance was 18·1 % (95 % CI 16·5, 19·8). When categorised broadly, grains, fruit, lactose, fish, vegetables, alcohol and nuts were most troublesome for individuals in that order. CONCLUSIONS: Self-reported food intolerance is common in US internet users. The effect of food on gastrointestinal symptoms and avoidant behaviours deserves further attention.