Systemic Consequences of Chronic Ethanol Intake

Authors

• Muni Swamy Ganjayi, Ohio Univ. Coll. of Osteopat. Med.
• Thomas A. Krauss, Ohio Univ. Coll. of Osteopat. Med.
• Gage E. Demster, Ohio Univ. Coll. of Osteopat. Med.
• Sehyung Park, University of Kentucky College of Medicine
• Garrett B. Anspach, University of Kentucky College of Medicine
• Sarah R. Anthony, Ohio State University
• Shaohua Wang, Ohio Univ. Coll. of Osteopat. Med.
• Michael Tranter, Ohio State University
• Robert N. Helsley, University of KentuckyFollow
• Cory W. Baumann, Ohio Univ. Coll. of Osteopat. Med.Follow

Abstract

Chronic ethanol (EtOH) consumption is a major contributor to multi-organ dysfunction, yet its systemic effects remain incompletely understood. To address this, we utilized a physiologically relevant long-term mouse model, administering 20% EtOH in drinking water for 60 weeks, to investigate the integrated consequences of chronic exposure. EtOH-consuming mice (0.4–0.5 mL/day) exhibited > 30% reductions in chow and fluid intake, resulting in a 12% decrease in total caloric intake compared to controls (p < 0.001). Body mass remained similar until Week 52, after which EtOH-treated mice had lower body mass due to reductions in both lean and fat mass (p ≤ 0.004). Functional assessments revealed impaired treadmill endurance (−17%) and grip strength (−11%) (p ≤ 0.037), while motor coordination remained unaffected (p = 0.203). Chronic EtOH exposure significantly altered gut microbiota composition, reducing Lactobacillus and enriching Faecalibaculum, Clostridium, and Bifidobacterium at the genus level. These changes were accompanied by marked depletion of short-chain fatty acids (p ≤ 0.05). Indirect markers of gut permeability (serum LPS & zonulin) and liver injury (serum ALT & AST, hepatic amyloid content) were elevated, alongside increased total cholesterol and > 62% upregulation of hepatic TNFα, IL-6 & serum amyloid A (p ≤ 0.046). EtOH also induced dyslipidemia and glucose intolerance (p ≤ 0.041), although transcriptomic changes in white adipose tissue were minimal despite elevated free fatty acids. In conclusion, chronic EtOH consumption disrupts energy balance, compromises gut barrier integrity, and impairs hepatic metabolism, collectively driving systemic and metabolic dysfunction. These findings underscore the gut-liver axis as a key mediator of EtOH-induced pathology and highlight the gut microbiome as a promising therapeutic target.

Document Type

Article

Publication Date

4-1-2026

Notes/Citation Information

Publisher Copyright: © 2026 The Author(s). Comprehensive Physiology published by Wiley Periodicals LLC on behalf of American Physiological Society.

Digital Object Identifier (DOI)

10.1002/cph4.70132

Archival?

Archival

Repository Citation

Ganjayi, Muni Swamy; Krauss, Thomas A.; Demster, Gage E.; Park, Sehyung; Anspach, Garrett B.; Anthony, Sarah R.; Wang, Shaohua; Tranter, Michael; Helsley, Robert N.; and Baumann, Cory W., "Systemic Consequences of Chronic Ethanol Intake" (2026). Markey Cancer Center Faculty Publications. 520.
https://uknowledge.uky.edu/markey_facpub/520