Two microbiota subtypes identified in Irritable Bowel Syndrome with distinct responses to the low-FODMAP diet

Abstract

Objective: Reducing FODMAPs can be clinically beneficial in IBS but the mechanism is poorly understood. We aimed to detect microbial signatures that might predict response to the low FODMAP diet and assess whether microbiota compositional and functional shifts could provide insights into its mode of action. Design: We used metagenomics to determine high-resolution taxonomic and functional profiles of the stool microbiota from IBS cases and household controls (n=56 pairs) on their usual diet. Clinical response and microbiota changes were studied in 41 pairs after 4 weeks on a low FODMAP diet. Results. Unsupervised analysis of baseline IBS cases pre-diet identified two distinct microbiota profiles, which we refer to as IBSP (pathogenic-like) and IBSH (health-like) subtypes. IBSP microbiomes were enriched in Firmicutes and genes for amino acid and carbohydrate metabolism, but depleted in Bacteroidetes species. IBSH microbiomes were similar to controls. On the low FODMAP diet IBSH and control microbiota were unaffected, but the IBSP signature shifted towards a health-associated microbiome with an increase in Bacteroidetes (p=0.009), a decrease in Firmicutes species (p=0.004) and normalization of primary metabolic genes. The clinical response to the low FODMAP diet was greater in IBSP subjects compared to IBSH (p = 0.02). Conclusion: 50% of IBS cases manifested a 'pathogenic' gut microbial signature. This shifted towards the healthy profile on the low FODMAP diet; and IBSP cases showed an enhanced clinical responsiveness to the dietary therapy. The effectiveness of FODMAP exclusion in IBSP may result from the alterations in gut microbiota and metabolites produced. Microbiota signatures could be useful as biomarkers to guide IBS treatment; and investigating IBSP species and metabolic pathways might yield insights regarding IBS pathogenic mechanisms.

Gut‐brain axis dysfunction underlies FODMAP‐induced symptom generation in irritable bowel syndrome

“…In addition to increased motility and luminal distension effects, other mechanisms at the level of the gut which cannot be measured using MRI, including mast cells, barrier dysfunction and intestinal microbiota may also be involved in FODMAP‐induced symptom generation 30,31 …”

Long‐term personalized low FODMAP diet in IBS

“…To account for strong placebo effect described in IBS patients, 19,20 multiple randomized controlled trials (RCTs) were performed to investigate the efficacy of the low FODMAP diet in comparison with the typical diet, the habitual diet, the high FODMAP diet, or the traditional/sham/alternative dietary advice. Most of these studies showed beneficial effects of the low FODMAP diet in IBS symptoms, 6,8,21‐25 and few studies observed similar treatment efficacy compared to a traditional dietary advice, 6,26 a general dietary advice, 27 yoga, 28 or hypnotherapy 29 . Furthermore, concerns were raised due to the restrictive nature of this diet, as nutritional adequacy might be at risk 30 .…”

“…In addition, pre‐existing fructose malabsorption, higher exhaled hydrogen after a nutrient challenge, and specific volatile compound profiles have been associated with better response to a low FODMAP diet 33‐35 . However, one of the most studied predictors of response to the diet is the microbiome, 21,23,32,36‐39 as long‐term diet is a major modulator of its composition and function.…”

“…In contrast to earlier studies that found increased abundance of certain bacteria only in non‐responders, the follow‐up studies identified higher levels of Bacteroides fragilis , Acinetobacter , Ruminiclostridium , Streptococcus , and Eubacterium 37 or higher saccharolytic capability and acetate levels, with lower level of butyric acid in the stools of the responders 23 . A very recent study suggested that the subset of patients with best response to the diet possessed a microbial profile termed “pathogenic” (IBS P ) for its potentially pathogenic properties, harboring high levels of C. difficile , C. sordellii and C. perfringens , Faecalicatena gnavus , C. clostridioforme and Fusicatenibacter saccharivorans , and low levels of Bacteroides spp 21 . At the functional level, the IBS P microbiome was enriched in pathways involved in amino acid biosynthesis and carbohydrate metabolism 21 .…”

“…A very recent study suggested that the subset of patients with best response to the diet possessed a microbial profile termed “pathogenic” (IBS P ) for its potentially pathogenic properties, harboring high levels of C. difficile , C. sordellii and C. perfringens , Faecalicatena gnavus , C. clostridioforme and Fusicatenibacter saccharivorans , and low levels of Bacteroides spp 21 . At the functional level, the IBS P microbiome was enriched in pathways involved in amino acid biosynthesis and carbohydrate metabolism 21 . And finally, a recent meta‐analysis suggested that a low FODMAP diet would be recommendable to patients with high colonic methane and SCFA production 39 .…”