Combining vitamin E metabolite 13'-carboxychromanol and a lactic acid bacterium synergistically mitigates colitis and colitis-associated dysbiosis in mice

Synbiotics may be useful to mitigate intestinal diseases such as ulcerative colitis. Here we show that combining 13'-carboxychromanol (δT3-13'), a metabolite of vitamin E δ-tocotrienol (δT3) via omega-oxidation, and Lactococcus lactis subsp. cremori (L. cremoris), but neither agent alone, significantly attenuated dextran sulfate sodium (DSS)-induced fecal bleeding and diarrhea, histologic colitis and interleukin 1β in mice. The combination of δT3-13'+L. cremoris also synergistically prevented DSS-caused compositional changes in gut microbiota and enriched beneficial bacteria including Lactococcus and Butyricicoccus. Interestingly, the anti-colitis effect correlated with the concentrations of δT3-13'-hydrogenated metabolite that contains 2 double bonds on the side chain (δT2-13'), instead of δT3-13' itself. Moreover, in contrast to δT3-13', combining δT3 and L. cremoris showed modest anti-colitis effects and did not prevent colitis-associated dysbiosis. In addition, ex vivo anaerobic incubation studies revealed that gut microbes selected by δT3-13' in the animal study could metabolize this compound to δT2-13' via hydrogenation, which appeared to be enhanced by L. cremoris. Overall, our study demonstrates that combining δT3-13' and L. cremoris can synergically prevent dysbiosis, and may be a novel synbiotic against colitis potentially via promoting δT3-13' metabolizers, which in turn contributes to superior beneficial effects of the combination.