2'-Fucosyllactose modulates gut microbiota and systemic metabolism in mild-to-moderate ulcerative colitis: a randomized crossover trial.

The gut microbiota in active ulcerative colitis (UC) differs from that of healthy individuals. Human milk oligosaccharides (HMOs) are prebiotics found in human breastmilk which promote infant health, but are lesser studied in adults. The objective of this study was to assess the impact of the HMO 2'-fucosyllactose (2'-FL) on symptoms, inflammation, gut microbiota, and systemic metabolism in mild-to-moderate UC. In this randomized, double-blind, placebo-controlled crossover clinical trial, 38 patients with mild-to-moderate UC were randomized to receive 28 days of 2'-FL or 28 days of maltodextrin placebo, followed by washout and crossover. Patient-reported outcome measures, feces, urine, and serum samples were collected before and after each intervention, and after a final washout period. Although no clear treatment effect was observed on conventional clinical indices, 2'-FL exposure was associated with improved patient-reported disease control. 2'-FL significantly modulated the gut microbiota, markedly increasing Bifidobacterium abundance (effect size 4.4%, 95% CI 2.33%-6.47%, P = 6.5 × 10-5). Fecal metabolite profiles showed changes consistent with altered microbial carbohydrate metabolism. Exploratory analyses suggested that age and baseline microbiota may influence clinical and biological responsiveness to 2'-FL. 2'-FL exposure was associated with improvement in patient-reported disease control, gut microbiota modulation, and cross-compartmental host-microbial metabolic profile modifications; Clinicaltrials.gov number, NCT06050811.