Modulation of Microbiota-Derived Bile Acids Linked to Symptom Amelioration in Crohn's Disease: Insights From a Randomized Clinical Trial With Xanthohumol Supplementation.

Xanthohumol (XN), a dietary flavonoid from hops (Humulus lupulus), possesses anti-inflammatory and microbiome-modulatory properties with potential therapeutic benefits for Crohn's disease (CD). To investigate the effects of XN on the gut environment in CD, we conducted a randomized, placebo-controlled clinical trial-the XN Microbiome and Signature (XMaS) trial (NCT4590508). 19 participants with clinically active CD completed the study. They were randomized to receive 24 mg/day of XN or placebo for 8 weeks, with clinical assessments at baseline and every 2 weeks. We assessed changes to Crohn's disease activity index (CDAI) scores, systemic inflammation, gut barrier function, profiling of microbial metabolism of XN, and gut microbiota composition and metabolism. Integration analysis of gut microbiota abundance, fecal metabolites, and inflammatory markers with CDAI scores revealed a pattern in which reductions in secondary bile acids and increases in IL-10 were associated with improved CDAI score in XN-treated individuals. These findings suggest that XN beneficially modulates the gut environment in CD by influencing microbial bile acid metabolism and host inflammatory response, thereby improving symptoms in individuals with severe innate immune activation.