Vitamin E delta-tocotrienol and metabolite 13'-carboxychromanol inhibit colitis-associated colon tumorigenesis and modulate gut microbiota in mice.
Academic Article
Overview
Research
Identity
Additional Document Info
Other
View All
Overview
abstract
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.
