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. [Display omitted] • Combining lactic acid bacteria and vitamin E metabolite δT3-13′ is a novel synbiotic. • This combination synergistically mitigated experimental colitis in mice. • This combination prevented colitis-caused dysbiosis and promoted beneficial bacteria. • Gut microbes can metabolize δT3-13′ via hydrogenation. • δT3-13′ promoted its metabolizers, which were enhanced by lactic acid bacteria. [ABSTRACT FROM AUTHOR]