# Acetate reprograms gut microbiota during alcohol consumption

## TL;DR

This study shows that gut microbiota changes from alcohol consumption are caused by acetate, not direct ethanol metabolism.

## Contribution

The paper reveals that ethanol is not directly metabolized by gut microbes, but acetate levels drive microbiota changes.

## Key findings

- Ethanol is not directly metabolized by gut microbiota under anaerobic conditions.
- Ethanol-feeding activates acetate dissimilation in the gut microbiota.
- Elevated acetate levels, not ethanol, drive microbiota alterations in mice.

## Abstract

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 use isotope labeled [1-13C] ethanol, metagenomics, and metatranscriptomics in ethanol-feeding and intragastric mouse models to investigate the metabolic impacts of alcohol consumption on the gut microbiota. First, we show that although stable isotope labeled [1-13C] ethanol contributes to fatty acid pools in the liver, plasma, and cecum contents of mice, there is no evidence of ethanol metabolism by gut microbiota ex vivo under anaerobic conditions. Next, we observe through metatranscriptomics that the gut microbiota responds to ethanol-feeding by activating acetate dissimilation, not by metabolizing ethanol directly. We demonstrate that blood acetate concentrations are elevated during ethanol consumption. Finally, by increasing systemic acetate levels with glyceryl triacetate supplementation, we do not observe any impact on liver disease, but do induce similar gut microbiota alterations as chronic ethanol-feeding in mice. Our results show that ethanol is not directly metabolized by the gut microbiota, and changes in the gut microbiota linked to ethanol are 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.

Chronic alcohol use is associated with intestinal bacterial overgrowth and dysbiosis, but the contribution of ethanol is unclear. Here, using mouse models, the authors find that ethanol is not directly metabolized by the gut microbiota, and that induced changes are rather a side effect of elevated acetate levels.