Polyguluronate alleviates ulcerative colitis by targeting the gut commensal Lactobacillus murinus and its anti-inflammatory metabolites

Polyguluronate (PG) is a fermentable polysaccharide from edible algae. The present study was designed to investigate the therapeutic effect of PG on ulcerative colitis (UC) and its underlying mechanisms. Our results suggest that oral intake of PG attenuates UC and improves gut microbiota dysbiosis by promoting the growth of Lactobacillus spp. in dextran sulfate sodium-fed mice. Five different species of Lactobacillus were isolated from the feces of PG-treated mice and L. murinus was identified to have the best anti-colitis effect, suggesting a critical role for L. murinus in mediating the therapeutic effect of PG. Furthermore, PG was degraded potentially by the beta-glucuronidase from L. murinus and adding PG to the culture medium of L. murinus remarkably increased its production of anti-inflammatory metabolites, including itaconic acid, cis-11,14-eicosadienoic acid, and 3-amino-3-(2-chlorophenyl)-propionic acid. Additionally, L. salivarius, a human intestine-derived PG-utilizing species that is closely related to L. murinus, was also demonstrated to have potent anti-colitis effects, suggesting that it is a candidate target of PG in the human gut. Altogether, our study illustrates an unprecedented application of PG in the treatment of UC and establishes the basis for understanding its therapeutic effect from the perspective of L. murinus and its metabolites.