Gut Microbiome Composition and Function, Diet and Clinical Factors in Relation to Fermentable Carbohydrate-Induced Bloating: A Double-Blind, Randomized, Crossover Trial.

Abstract

Specific foods are associated with abdominal bloating, which can significantly impact quality of life. To identify responders to fiber-induced bloating and the mechanisms underpinning clinical and microbial responses. Double-blind, placebo-controlled, randomized, 2-period, 2-challenge crossover trial in 41 individuals with functional bloating. Participants were randomized to 8 g/d of fructan or α-galacto-oligosaccharides (α-GOS) for 7 days with a 21-day washout. Clinical, nutritional, microbial (shotgun sequencing, metatranscriptomics) and fermentation (short-chain fatty acids, volatile organic compounds, breath hydrogen) profiles were characterized prior to each challenge to identify factors predicting response, and after the challenge to elucidate mechanisms underpinning food-induced bloating. Thirty-nine participants completed both challenges (39 fructan, 40 α-GOS). Overall, seven (7/39, 17.9%) participants were fructan responders and eight (8/40, 20%) were α-GOS responders (experienced fiber-related symptom induction). Clinical metrics indicative of bloating distinguished responders and non-responders to both challenges, including greater abdominal girth (fructan, p = 0.009; α-GOS, p = 0.030). α-GOS responders had higher breath hydrogen (H2) pre-challenge than α-GOS non-responders (p = 0.011). Trends were identified within metagenomic and metatranscriptomic gut microbial analyses, with higher carbohydrate active enzyme (CAZyme) diversity in fructan responders (pre-challenge, adjusted p-value (padj) = 0.024; post-challenge, padj = 0.042), and greater increase in gene expression for gamma-aminobutyric acid (GABA) degradation in α-GOS responders (padj = 0.041). A higher burden of GI symptoms predicts clinical response to fermentable fibers in functional bloating, while for α-GOS, higher repeated fasting breath H2 is also a predictor. Gut microbiome function and fermentation is associated with functional bloating; however, further investigations are required to draw firm conclusions for the microbial influence in this interplay.ClinicalTrials.gov (Identifier: NCT04802798).