Archived

This content is available here for research, reference, and/or recordkeeping.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.

Document Type

Article

Publication Date

2026

Notes/Citation Information

© 2026 Blanton, Napier, Keen, Stuart, Cinco, Hemati, Bruntz, Wilson, Barnes, Khadka, Grant and Messaoudi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Digital Object Identifier (DOI)

https://doi.org/10.3389/fmicb.2026.1794794

Funding Information

The author(s) declared that financial support was received for this work and/or its publication. This work was supported by NIH 1R01AA028735-01 (Messaoudi), 5U01AA013510-20 (Grant), and 2R24AA019431-11 (Grant). MB is supported by NIH 1F31AA031600-01A1. EN is supported by NIH T32 AA027488.

Download

Share

COinS