The Role of UC-Associated Microbiota in Fiber Fermentation and Tolerance

Objectives: Patients with ulcerative colitis (UC) often restrict fiber intake due to poor tolerance. Furthermore, how dietary fibers interact with dysbiotic microbiomes and whether their functional capacity is conserved remain unclear. This study aimed to determine fiber physicochemical property(ies) that dictate efficacy and tolerance in healthy and UC-associated microbiotas.

Methods: Four dietary fibers—high-methoxyl pectin (HMP), chicory inulin (ChIn), resistant maltodextrin (RMD), and wheat bran (WB)—differing in solubility, structural complexity, and fermentation rate, were evaluated. After simulated gastrointestinal digestion (INFOGEST), fibers were fermented with fecal microbiota from two healthy donors and two pediatric donors with UC. Patients were stratified into moderate (1,195 µg/g) and severe (3,000 µg/g) groups based on fecal calprotectin. Samples were incubated for 6, 12, 24, and 48 h. SCFAs, pH, and gas production were measured. The V4 region of the 16S rRNA gene was sequenced on a MiniSeq.

Results: UC-associated microbiota exhibited lower fermentation capacity, particularly under severe dysbiosis. HMP produced the highest SCFA levels at 24-48 h in moderate UC and at 48 h in severe UC. Surprisingly, the linear fructan ChIn failed to stimulate robust fermentation in the UC cohorts despite its high fermentability in healthy groups. No butyrate production was detected in severe UC. HMP in moderate UC reached SCFA concentrations comparable to those of healthy donors by 48 h, without excess gas production. HMP enriched primary fiber degraders in moderate UC (e.g., Lachnospira). However, as disease severity increased, butyrate-producing taxa (e.g., Faecalibacterium) were depleted, explaining why butyrate production was not restored.

Conclusions: Dietary fiber fermentation was modulated by disease severity and substrate structural complexity. These findings challenge the use of generalized fiber supplementation and underscore the need for stratified nutritional interventions based on disease severity.

Funding: Whistler Center for Carbohydrate Research and the Ralph W. and Grace M. Showalter Research Trust Award.