Acetate reprograms gut microbiota during alcohol consumption

Liver damage due to chronic alcohol use is among the most prevalent liver diseases. Alcohol consumption frequency is a strong factor of microbiota variance. Here, we investigated whether changes are caused by ethanol metabolism by the gut microbiota. Although stable isotope labeled [1-13C] ethanol contributes to fatty acid pools in the liver, plasma, and cecum contents of mice, we found no evidence of ethanol metabolism by gut microbiota ex vivo under anaerobic conditions. Metatranscriptomics revealed that the gut microbiota responded to ethanol-feeding by activating acetate dissimilation, not by metabolizing ethanol directly. Blood acetate concentrations were elevated during ethanol consumption. Increasing systemic acetate levels with glyceryl triacetate supplementation did not affect liver disease, but induced similar gut microbiota alterations as chronic ethanol-feeding in mice. Our results suggest that ethanol is not directly metabolized by the gut microbiota, and changes in the gut microbiota linked to ethanol are actually a side effect of elevated acetate levels. De-trending for these acetate effects may be critical for understanding gut microbiota changes that cause alcohol-related liver disease, just as it has been shown in other diseases such as diabetes.