Unfermented b-fructan Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are affected by dietary factors, including nondigestible carbohydrates (fibers), which are fermented by colonic microbes. Fibers are overall beneficial, but not all fibers are alike, and some patients with IBD report intolerance to fiber consumption. Given repro-ducible evidence of reduced fiber-fermenting microbes in patients with IBD, we hypothesized that fibers remain intact in select pa-tients with reduced fiber-fermenting microbes and can then bind host cell receptors, subsequently promoting gut inflammation. METHODS: Colonic biopsies cultured ex vivo and cell lines in vitro were incubated with oligofructose (5 g/L), or fermentation su-pernatants (24-hour anaerobic fermentation) and immune re-sponses (cytokine secretion [enzyme-linked immunosorbent assay/meso scale discovery] and expression [quantitative poly-merase chain reaction]) were assessed. Influence of microbiota in mediating host response was examined and taxonomic classifi- cation of microbiota was conducted with Kraken2 and metabolic profiling by HUMAnN2, using R software. RESULTS: Unfermented dietary b-fructan fibers induced proinflammatory cytokines in a subset of IBD intestinal biopsies cultured ex vivo, and immune cells (including peripheral blood mononuclear cells). Results were validated in an adult IBD randomized controlled trial examining b- fructan supplementation. The proinflammatory response to intact b-fructan required activation of the NLRP3 and TLR2 pathways. Fermentation of b-fructans by human gut whole microbiota cul-tures reduced the proinflammatory response, but only when mi-crobes were collected from patients without IBD or patients with inactive IBD. Fiber-induced immune responses correlated with microbe functions, luminal metabolites, and dietary fiber avoidance. CONCLUSION: Although fibers are typically beneficial in individuals with normal microbial fermentative potential, some dietary fibers have detrimental effects in select patients with active IBD who lack fermentative microbe activities. The study is publicly accessible at the U.S. National Institutes of Health data-base (clinicaltrials.gov identification number NCT02865707).