Vitamin E delta-tocotrienol and metabolite 13'-carboxychromanol inhibit colitis-associated colon tumorigenesis and modulate gut microbiota in mice.
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The gut microbiota play important roles in colon cancer. Vitamin E -tocotrienol (TE) and its metabolite TE-13'-carboxychromanol (TE-13') are known to have cancer-preventive effects, but their impact on gut flora during tumorigenesis and the role of the metabolite in TE's beneficial effects remain to be determined. In the murine colitis-associated colon cancer (CAC) induced by azoxymethane (AOM) and dextran sulfate sodium (DSS), we show that TE and TE-13' inhibited the multiplicity of large adenomas (>2 mm2) by 34% (P<.05) and 55% (P<.01), respectively, compared to the control diet. TE-13' diminished AOM/DSS-increased GM-CSF and MCP-1, and TE decreased IL-1. Using 16S rRNA gene sequencing of fecal DNAs, we observe that TE and TE-13' modulated the composition but not the richness of gut microbes compared to the control. Both TE and TE-13' enhanced potentially beneficial Lactococcus and Bacteroides. The elevation of Lactococcus positively correlated with fecal concentrations of TE-13' and its hydrogenated metabolite, suggesting that the metabolite may contribute to TE's modulation of gut microbes. Furthermore, TE-13' counteracted AOM/DSS-induced depletion of Roseburia that is known to be decreased in patients with inflammatory bowel diseases. TE uniquely elevated (Eubacterium) coprostanoloigenes. Our study demonstrates that TE and TE-13' inhibited tumorigenesis, suppressed pro-inflammatory cytokines and modulated gut microbiota in a murine CAC model. These findings uncover new and distinct activities of TE and TE-13' and support the notion that the metabolite may play a role in TE's anticancer and modulation of gut microbes.
author list (cited authors)
Yang, C., Zhao, Y., Im, S., Nakatsu, C., Jones-Hall, Y., & Jiang, Q.
complete list of authors
Yang, Chao||Zhao, Yiying||Im, Suji||Nakatsu, Cindy||Jones-Hall, Yava||Jiang, Qing