Drinking pattern and sex modulate the impact of ethanol consumption on the mouse gut microbiome

Author(s)

Brigagao Pacheco da Silva, Carla ; Nascimento-Silva, Edson Alexandre ; Zaramela, Livia Soares ; da Costa, Bruno Ruiz Brandao ; Rodrigues, Vanessa Fernandes ; De Martinis, Bruno Spinosa ; Carlos, Daniela ; Tostes, Rita C.

• Document type: Journal article
• Source: Physiological Genomics; v. 57, n. 3, p. 16-pg., 2025-03-07.

Abstract

Gut microbiota impacts host homeostasis and diseases. Chronic plus binge ethanol consumption has been linked to increased injuries than chronic or binge ethanol intake alone. We hypothesized that distinct shapes in gut microbiota composition are induced by chronic, binge, and the association of these treatments, thereby affecting host functions and contributing to sex-based differences in alcohol use disorders. Male and female C57BL/6J mice were submitted to chronic, binge, or chronic plus binge ethanol feeding. DNA was extracted from fecal microbiota, followed by analysis of the V3-V4 region of the 16S rRNA gene and sequencing on an Illumina platform. Gut microbiome analysis was performed using QIIME v2022.2.0. Functional profiling of the gut microbiome was performed using PICRUSt2. Ethanol differentially affected the gut microbiota of female and male mice. Decreased alpha diversity was observed in male and female mice from the chronic plus binge and chronic groups, respectively. The genera Faecalibaculum, Lachnospiraceae, and Alistipes were identified as major potential biomarkers for gut dysbiosis induced by ethanol consumption. In addition, ethanol-induced gut dysbiosis altered several metabolic pathways. Ethanol consumption modifies the mouse gut microbiome in a drinking pattern- and sex-dependent manner, potentially leading to different susceptibility to ethanol-related diseases. Chronic plus binge ethanol intake induces a more pronounced gut dysbiosis in male mice. Conversely, chronic ethanol is linked to a greater degree of gut dysbiosis in female mice. The changed gut microbiome may be potentially targeted to prevent, mitigate, or treat alcohol use disorders. NEW & NOTEWORTHY Ethanol alters the mouse gut microbiome in a drinking pattern- and sex-dependent manner. Chronic plus binge ethanol intake induces a more severe gut dysbiosis in male mice, whereas chronic ethanol consumption appears to be a more potent inductor of gut dysbiosis in female mice. Ethanol-induced gut dysbiosis alters several pathways linked to metabolism, genetic and environmental information processing, cellular processes, organism systems, and neurological human diseases. (AU)

• FAPESP's process: 20/08554-9 - Establishment of an experimental and computational platform to study host-microbes interactions promoted by sialic acids
• Grantee: Lívia Soares Zaramela
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/11339-2 - Trimethylamine N-oxide (TMAO) as a link among gut dysbiosis, immune system activation and vascular dysfunction induced by ethanol consumption
• Grantee: Carla Brigagão Pacheco da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC