Oral supplementation with sesaminol, a sesame-related lignan, ameliorates ethanol-induced dysbiosis of the gut microbiota and increases the gut luminal short-chain fatty acid concentrations of mice

Chronic ethanol consumption significantly increases the risk of colorectal cancer. The pathogenesis of ethanol-related colorectal cancer involves oxidative stress and inflammation induced by ethanol in the colon and rectum, as well as dysfunction of the gut barrier and greater intestinal permeability. Previously, we demonstrated that chronic oral ethanol administration in mice leads to dysbiosis of the fecal microbiota, similar to that which characterizes human inflammatory bowel disease. In addition, this ethanol-induced gut pathophysiology was alleviated by the oral administration of sesaminol, a lignan derived from sesame that is known for its potent antioxidant activity. In the present study, we investigated the effects of oral sesaminol administration on the fecal microbiota and short-chain fatty acid (SCFA) profiles of mice that were chronically orally administered ethanol or not. Chronic ethanol administration reduced the abundances of fecal bacterial taxa that produce butyric acid, thereby reducing the fecal butyric acid content. The oral administration of sesaminol (2.5 mg/d) mitigated the ethanol-induced dysbiosis of the gut microbiota and increased the luminal SCFA content, and particularly that of butyric acid. The effects of oral sesaminol administration on ethanol-induced gut pathophysiology may be mediated, at least in part, by the anti-inflammatory and gut barrier–protective properties of butyric acid.