GUT MICROBIOTA–PHYTOCHEMICAL INTERACTIONS IN ULCERATIVE COLITIS: MECHANISTIC INSIGHTS AND THERAPEUTIC OPPORTUNITIES

The mucosal inflammatory network which drives ulcerative colitis involves a series of biological interactions between epithelial barrier injury, microbial dysbiosis, defective microbial metabolism, immune activation, oxidative stress and impaired restitutaion. The relevance of phytochemicals to this disease is not one of general “anti-inflammatory” activity, but rather by their ability to reach the colonic lumen at pharmacologically relevant concentrations, to undergo microbial biotransformation and to alter the output of microbial metabolites, and to act directly at epithelial and immune interfaces that define the pathology of ulcerative colitis. The most coherent evidence for translation into clinical practice for curcumin includes in combination with mesalamine, curcumin formulations enhanced by bioenhancing agents, resveratrol in small randomized trials, indigo naturalis, and Curcumin–QingDai. The best mechanistic evidence is based on microbial tryptophan metabolism, aryl hydrocarbon receptor signalling, interleukin 22 dependent epithelial repair, urolithin formation from ellagitannins, Nrf2 mediated redox defence, nuclear factor kappa B suppression, attenuation of the inflammasome, preservation of the mucus barrier, restoration of tight junctions and partial recovery of some short chain fatty acid producing microbial functions. In this review, we have collected the recent primary and translational studies available on microbiota/phytochemical interactions and merged them with compound-specific clinical and mechanistic evidence to suggest a development framework for precision medicine, including colonic exposure, microbial metabotype, mucosal pharmacodynamics, biomarker response, endoscopic healing, histology, and safety surveillance. The therapeutic window is optimum when phytochemicals are designed as colon targeted, microbiotically dependent pharmacologic interventions, instead of as broad-based anti-inflammatory dietary supplements.