Konjac glucomanan-mediated microbiota cross-feeding yields valeric acid for colitis mitigation

Abstract Ulcerative colitis is closely linked to gut dysbiosis, and konjac glucomannan (KGM) can ameliorate symptoms by modulating the gut microbiota. However, the specific microbial interactions driving these therapeutic effects remain unclear. This study aimed to identify a KGM-mediated microbial interaction and its role in alleviating colitis. Through in vitro fermentation, we discovered that KGM mediates a mutualistic interaction where Roseburia intestinalis NSP017 promotes the growth of Bacteroides xylanisolvens NSP016, leading to enhanced production of the metabolite valeric acid. These findings were validated in vivo using a DSS-induced colitis mouse model. Treatment with KGM and the two bacterial strains synergistically reduced disease severity, protected the intestinal barrier, and modulated the gut microbiota. Crucially, valeric acid production was dependent on the presence of R. intestinalis NSP017 and correlated with disease amelioration. Our findings establish a novel axis that KGM facilitates a functional interaction between R. intestinalis NSP017 and B. xylanisolvens NSP016, resulting in the generation of valeric acid, which functions as a key metabolite contributing to the improvement of colitis outcomes in mice.