Chronic alcohol consumption disrupts the gut microbial and metabolic landscapes

Alcohol use disorder (AUD) increases incidence of infections, organ damage, and cancers. Aberrant inflammation is likely a driver of these adverse outcomes. Indeed, chronic alcohol consumption (CAC) rewires macrophages/monocytes toward a hyper-inflammatory phenotype. Prior studies showed increased gut permeability and dysbiosis. Translocation of host- and microbial-derived metabolites could trigger the hyper-inflammatory responses generated by macrophages/monocytes. However, the exact changes in these metabolites remain poorly defined due to confounders that complicate clinical studies and the differences between human and rodent gut microbiomes.

Here, we utilized a non-human primate model of ethanol self-administration to characterize alcohol-induced alterations in gut microbes and associated metabolomes. The microbiome was analyzed with 16s rRNA sequencing while a combination of GC-MS and LC-MS was used to assess changes in metabolites. Monocyte function was determined using flow cytometry.

Twelve months of alcohol use led to a decrease in SCFA-producing bacteria and disruption of fatty acid and amino acid metabolites. Moreover, fecal metabolites obtained after 12 months of CAC heightened monocytes' inflammatory responses.

These findings indicate that CAC-induced gut dysbiosis contributes to changes in fecal and circulating metabolites, which in turn can lead to monocyte dysregulation, possibly via innate immune training-like mechanisms.