Fig. 5: Summary of three main experiments.

a Experiment one utilized oral gavage of labeled ethanol, in order to evaluate where it was being metabolized. From this, we found that ethanol is broken down in the liver to acetate which is then released into circulation with an increased pool forming in the gut. b Experiment two consistent of two stages. First, mice were fed a Lieber DeCarli diet for a total of 9 weeks after which the blood short chain fatty acids (SCFA) along with abundance and transcription of cecum microbiota were compared between conditions. Second, the cecum microbiota were collected and grown anaerobically in minimal media with or without ethanol. These experiments showed that anaerobic gut bacteria, in particular species of the phylum Bacteroidetes, do not break down ethanol to acetate but rather utilize acetate produced from the liver for gluconeogenesis. c Experiment three replicated acetate levels found in the gut during oral gavage of ethanol through the intragastric infusion of Glyceryl Triacetate (GTA) which increases gut acetate levels but not blood. For comparison, four conditions were performed being glucose vs. ethanol and glycerol vs. GTA in combination. The gut microbiota abundance, liver damage, blood SCFA, and gut acetate levels were measured. This experiment demonstrated that GTA causes similar alterations in the gut microbiome to that of ethanol, with increases in the phylum Bacteroidetes, but did not cause liver damage. Created with BioRender.com.