Abstract
Rationale
Increasing evidence has demonstrated that changes in the gut microbiome, including those associated with dietary influences, are associated with alterations in many physiological processes. Alcohol consumption is common across human cultures and is likely to have a major effect on the gut microbiome, but there remains a paucity of information on its effects in primates.
Objectives
The effects of chronic alcohol consumption on the primate gut microbiome and metabolome were studied in rhesus macaques that were freely drinking alcohol. The objectives of the study were to determine what changes occurred in the gut microbiome following long-term exposure to alcohol and if these changes were reversible following a period of abstinence.
Methods
Animals consuming alcohol were compared to age-matched controls without access to alcohol and were studied before and after a period of abstinence. Fecal samples from rhesus macaques were used for 16S rRNA sequencing to profile the gut microbiome and for metabolomic profiling using mass spectrometry.
Results
Alcohol consumption resulted in a loss of alpha-diversity in rhesus macaques, though this was partially ameliorated by a period of abstinence. Higher levels of Firmicutes were observed in alcohol-drinking animals at the expense of a number of other microbial taxa, again normalizing in part with a period of abstinence. Metabolomic changes were primarily associated with differences in glycolysis when animals were consuming alcohol and differences in fatty acids when alcohol-drinking animals became abstinent.
Conclusions
The consumption of alcohol has specific effects on the microbiome and metabolome of rhesus macaques independent of secondary influences. Many of these changes are reversed by a relatively short period of abstinence.
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Acknowledgements
The authors would like to thank the New England Primate Research Center Division of Veterinary Resources and all the animal care technicians for their assistance with sample collection. We would also like to thank Kristin Waraska and the Biopolymers Facility in the Harvard Medical School Department of Genetics and Ashley Johnson and Michael Garrett at the University of Mississippi Medical Center Genomics Core for support with next-generation sequencing.
Funding
These studies were funded by grant from the National Institutes of Health: OD011103, AA019688 (EJV), AA016179 (DMP), and AA016828 (DMP). The work performed through the University of Mississippi Medical Center Molecular and Genomics Facility is supported, in part, by funds from the National Institute of General Medical Sciences: GM103476, GM104357, and GM121334. The content of the manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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All animal studies were performed in accordance with the guidelines of the National Academies Guide for Care and Use of Laboratory Animals, Eighth Edition (National Research Council 2011). All protocols were approved by the Harvard Medical School Institutional Animal Care and Use Committee prior to commencement of animal studies.
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Zhang, X., Yasuda, K., Gilmore, R.A. et al. Alcohol-induced changes in the gut microbiome and metabolome of rhesus macaques. Psychopharmacology 236, 1531–1544 (2019). https://doi.org/10.1007/s00213-019-05217-z
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DOI: https://doi.org/10.1007/s00213-019-05217-z