1. Introduction
IBS, abdominal pain
INFLAMMATION, MINOR, IRRITABLE BOWEL SYNDROME (IBS), IRRITABLE BOWEL SYNDROME
Background: A mechanistic understanding of the effects of dietary treatment in irritable bowel syndrome (IBS) is lacking. Our aim was therefore to investigate how fermentable oligo- di-, monosaccharides, and polyols (FODMAPs) and gluten affected gut microbiota and circulating metabolite profiles, as well as to investigate potential links between gut microbiota, metabolites, and IBS symptoms. Methods: We used data from a double-blind, randomized, crossover study with week-long provocations of FODMAPs, gluten, and placebo in participants with IBS. To study the effects of the provocations on fecal microbiota, fecal and plasma short-chain fatty acids, the untargeted plasma metabolome, and IBS symptoms, we used Random Forest, linear mixed model and Spearman correlation analysis. Results: FODMAPs increased fecal saccharolytic bacteria, plasma phenolic-derived metabolites, 3-indolepropionate, and decreased isobutyrate and bile acids. Gluten decreased fecal isovalerate and altered carnitine derivatives, CoA, and fatty acids in plasma. For FODMAPs, modest correlations were observed between microbiota and phenolic-derived metabolites and 3-indolepropionate, previously associated with improved metabolic health, and reduced inflammation. Correlations between molecular data and IBS symptoms were weak. Conclusions: FODMAPs, but not gluten, altered microbiota composition and correlated with phenolic-derived metabolites and 3-indolepropionate, with only weak associations with IBS symptoms. Thus, the minor effect of FODMAPs on IBS symptoms must be weighed against the effect on microbiota and metabolites related to positive health factors.Irritable bowel syndrome (IBS) is a common condition affecting around 3–5 percent of the population in Western countries and is defined according to the Rome IV criteria by recurring abdominal pain in relation to stool irregularities [A gluten-free diet has also been advocated for alleviation of IBS symptoms, but results from clinical trials are inconsistent [Combining omics measurements at multiple levels of biology, i.e., multiomics, has emerged as an approach for studying complex biological processes [We have previously performed a double-blind, placebo-controlled, randomized three-way crossover trial with week-long interventions with FODMAPs, gluten or placebo in people with IBS by estimating symptoms with the IBS severity scoring system (IBS-SSS) [Since there are inconsistencies in the effects of FODMAPs and gluten on microbiota and SCFAs, and there is also a general lack of multiomics analysis in IBS and dietary trials, the aim of the present exploratory work was to investigate the effects of FODMAPs, gluten or placebo on both gut microbiota composition, fecal and plasma SCFAs and their relationship to IBS symptoms and the metabolome. We hypothesized that the FODMAP challenge would affect gut microbiota composition and that specific genera would be correlated with metabolites derived from dietary fiber fermentation and plant-based foods, including SCFAs, bile acids, phenolics and indole compounds. Furthermore, we hypothesized that such alterations might be related to IBS symptoms, as weakly indicated in previous studies [