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Concurrent gut transcriptome and microbiota profiling following chronic ethanol consumption in nonhuman primates
Tasha Barr1, Suhas Sureshchandra2, Paul Ruegger3
1a Division of Biomedical Sciences, University of California-Riverside , Riverside , CA , USA.
Chronic alcohol consumption in nonhuman primates alters gut gene expression and bacterial composition, potentially preceding alcohol-related diseases like colorectal cancer.
Area of Science:
- Gastroenterology and Hepatology
- Microbiology
- Oncology
Background:
- Alcohol use disorder (AUD) is linked to intestinal issues and increased colorectal cancer (CRC) risk.
- Current research limitations stem from reliance on short-term animal models and AUD patients with alcoholic liver disease (ALD).
- The specific effects of chronic alcohol intake on the gut, independent of liver disease, are not well understood.
Purpose of the Study:
- To investigate the impact of chronic, voluntary ethanol consumption on the primate intestinal tract.
- To identify changes in gene expression and gut microbiota composition in the absence of overt liver or colorectal cancer.
- To explore potential early biomarkers for alcohol-induced gut pathologies.
Main Methods:
- Utilized a nonhuman primate model (rhesus macaques) with voluntary ethanol self-administration for 12 months.
- Performed RNA-Seq and 16S rRNA gene sequencing on intestinal biopsies (duodenum, jejunum, ileum, colon).
- Analyzed data from 4 control and 8 ethanol-consuming macaques.
Main Results:
- Chronic ethanol consumption altered gene expression related to protein trafficking, metabolism, inflammation, and CRC development.
- Observed shifts in the relative abundance of gut bacteria, including potentially beneficial and inflammation/CRC-associated species.
- These molecular and microbial changes occurred in animals without clinical signs of ALD or CRC.
Conclusions:
- Chronic ethanol intake induces significant changes in intestinal gene expression and microbiota composition.
- These alterations may precede the clinical manifestation of alcohol-related gastrointestinal diseases.
- Identified potential early biomarkers for gut homeostasis disruption in AUD, aiding future intervention strategies.
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