Dietary α-mangostin, a xanthone from mangosteen fruit, exacerbates experimental colitis and promotes dysbiosis in mice

Scope: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. alpha-Mangostin (alpha-MG), the most abundant xanthone in mangosteen fruit, exerts anti-inflammatory and antibacterial activities in vitro. We evaluated the impact of dietary alpha-MG on murine experimental colitis and on the gut microbiota of healthy mice. Methods and results: Colitis was induced in C57BL/6J mice by administration of dextran sulfate sodium (DSS). Mice were fed control diet or diet with alpha-MG (0.1%). alpha-MG exacerbated the pathology of DSS-induced colitis. Mice fed diet with alpha-MG had greater colonic inflammation and injury, as well as greater infiltration of CD3(+) and F4/80(+) cells, and colonicmyeloperoxidase, than controls. Serum levels of granulocyte colony-stimulating factor, IL-6, and serum amyloid A were also greater in alpha-MG-fed animals than in controls. The colonic and cecal microbiota of healthy mice fed alpha-MG but no DSS shifted to an increased abundance of Proteobacteria and decreased abundance of Firmicutes and Bacteroidetes, a profile similar to that found in human UC. Conclusion: alpha-MG exacerbated colonic pathology during DSS-induced colitis. These effects may be associated with an induction of intestinal dysbiosis by alpha-MG. Our results suggest that the use of alpha-MG-containing supplements by patients with UC may have unintentional risk.