Depletion of Gut Microbiota Suppresses the Metabolite Formation of Vitamin E Forms Including Delta-tocotrienol and Its Long-chain Metabolite 13’-carboxychromanol in Mice

Abstract Objectives We recently show that supplementation of delta-tocotrienol (δTE), a vitamin E form and its metabolite δTE-13’-carboxychromanol (δTE-13’) modulated gut microbiota and meanwhile increased metabolites in feces. Since gut microbiota has been shown to metabolize phenolic compounds, we hypothesize that gut bacteria may play a role in metabolizing δTE and δTE-13’. This hypothesis was addressed in the comparison of metabolites formation between antibiotic cocktail (ABX)-treated mice and non-ABX treated mice. Methods Male Balb/c mice were given ABX or water daily for 7 days to remove the gut microbiota. Subsequently ABX or water-treated mice were given a single gavage of δTE/gamma-tocotrienol (δTE/γTE at 8:1) or δTE-13’ at 42mg/kg bw. 24-hr later, mice were sacrificed. We collected 24-hr accumulative fecal samples, adipose, plasma, colon and liver tissues and quantified the concentrations of vitamin E forms and metabolites in these samples. Results Compared with non-ABX controls, ABX-treated mice had decreased weights of liver, spleen and colon, while had doubled the amount of 24-hr fecal output. In δTE-gavaged animals, ABX treatment decreased fecal amounts of δTE and its metabolites by 61% and 98% respectively, while increased δTE level in the adipose tissue. Similarly, in animals gavaged with δTE-13’, ABX treatment led to a 98% reduction in its downstream metabolites. Additionally, ABX treatment decreased fecal excretion of metabolites from other vitamin E forms including α, γ, δ-tocopherols and γTE. Conclusions These results demonstrate that without the gut microbiota, fecal concentrations of vitamin E metabolites declined dramatically, suggesting potential role of the gut microbiota in metabolizing vitamin E forms. Funding Sources Purdue Center for Cancer Research.