Short‐Term Alcohol Consumption Is Sufficient to Disrupt Microbial Communities and the Intestinal and Circulating Metabolites in a Non‐Human Primate Model

The gut microbiome is a complex and dynamic community of microorganisms that play a crucial role in maintaining host health and facilitating inter-organ communication. The microbiome is altered by the exposome, a phenomenon known as dysbiosis. Alcohol misuse can disrupt the gut microbial community in a dose- and duration-dependent manner. Previous studies showed that chronic alcohol misuse can induce intestinal hyperpermeability and significantly shift microbial communities. However, these data were obtained primarily from cross-sectional clinical and rodent-based studies following long-term chronic alcohol consumption. Clinical studies often utilize samples from patients with alcoholic liver disease and are confounded by variability in factors that can modulate the microbiome and reliance on self-reported data. The intestinal cellular and microbial composition of rodent models differs significantly from that of humans, limiting the clinical translation of those findings. Therefore, the impact of alcohol misuse on the gut microbial communities and their metabolic implications remains poorly understood. Since rhesus macaques share significant genetic/physiological traits, as well as gut microbial communities, with humans, we assessed the impact of 6 months of voluntary daily alcohol consumption on the gut microbiome and its implications for the circulating and intestinal metabolomes. We report that short-term drinking induces dynamic changes in the abundance of short-chain fatty acid producers and increases microbes associated with the negative regulation of inflammation. Finally, altered fatty- and amino-acid metabolite signatures were observed. Taken together, these data enhance our understanding of the longitudinal implications of alcohol use.