Gut microbiome and metabolome in a non-human primate model of chronic excessive alcohol drinking.

Study Author Daria Piacentino, M.D., Ph.D., M.Sc.

Featured Paper of the Month – February 2022

Published in Translational Psychiatry by Daria Piacentino and Lorenzo Leggio, et al. of the NIDA IRP Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section.

Summary

Chronic excessive alcohol drinking causes more than 80,000 deaths in the U.S. each year. The gut microbiota, which hosts more than a trillion bacteria, is gaining increasing attention as a potential modulator in neuropsychiatric disorders. Its diversity is fundamental in maintaining homeostasis. There is limited research on the role of the microbiome-gut-brain axis in alcohol use disorder. Dr. Daria Piacentino and her colleagues address the fundamental question on whether chronic excessive alcohol drinking affects the gut microbiome and metabolome in a baboon model, investigated under rigorous controlled experimental conditions. The Authors show that changes in the gut microbiome and metabolome occur after significant long-term (12 years on average), but not relatively short-term (three years on average) excessive drinking. These changes include a detrimental decrease in gut microbiome diversity and alcohol-induced alterations of microbiota-related metabolites, such as aromatic amino acids, tricarboxylic acid cycle, and pentose. An increase in mucosal damage and oxidative stress markers was also observed. In conclusion, this work provides novel information on the effects of alcohol on the gut microbiome and metabolome and, importantly, helps bridge the translational gap in alcohol research between rodents and humans.

Publication Information

Piacentino, Daria; Grant-Beurmann, Silvia; Vizioli, Carlotta; Li, Xiaobai; Moore, Catherine F; Ruiz-Rodado, Victor; Lee, Mary R; Joseph, Paule V; Fraser, Claire M; Weerts, Elise M; Leggio, Lorenzo

Gut microbiome and metabolome in a non-human primate model of chronic excessive alcohol drinking Journal Article

In: Transl Psychiatry, vol. 11, no. 1, pp. 609, 2021, ISSN: 2158-3188.

Abstract | Links

@article{pmid34853299,

title = {Gut microbiome and metabolome in a non-human primate model of chronic excessive alcohol drinking},

author = {Daria Piacentino and Silvia Grant-Beurmann and Carlotta Vizioli and Xiaobai Li and Catherine F Moore and Victor Ruiz-Rodado and Mary R Lee and Paule V Joseph and Claire M Fraser and Elise M Weerts and Lorenzo Leggio},

url = {https://pubmed.ncbi.nlm.nih.gov/34853299/},

doi = {10.1038/s41398-021-01728-6},

issn = {2158-3188},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Transl Psychiatry},

volume = {11},

number = {1},

pages = {609},

abstract = {A relationship between the gut microbiome and alcohol use disorder has been suggested. Excessive alcohol use produces changes in the fecal microbiome and metabolome in both rodents and humans. Yet, these changes can be observed only in a subgroup of the studied populations, and reversal does not always occur after abstinence. We aimed to analyze fecal microbial composition and function in a translationally relevant baboon model of chronic heavy drinking that also meets binge criteria (drinking too much, too fast, and too often), i.e., alcohol ~1 g/kg and blood alcohol levels (BALs) ≥ 0.08 g/dL in a 2-hour period, daily, for years. We compared three groups of male baboons (Papio anubis): L = Long-term alcohol drinking group (12.1 years); S = Short-term alcohol drinking group (2.7 years); and C = Control group, drinking a non-alcoholic reinforcer (Tang®) (8.2 years). Fecal collection took place during 3 days of Drinking (D), followed by a short period (3 days) of Abstinence (A). Fecal microbial alpha- and beta-diversity were significantly lower in L vs. S and C (p's < 0.05). Members of the commensal families Lachnospiraceae and Prevotellaceae showed a relative decrease, whereas the opportunistic pathogen Streptococcus genus showed a relative increase in L vs. S and C (p's < 0.05). Microbiota-related metabolites of aromatic amino acids, tricarboxylic acid cycle, and pentose increased in L vs. S and C (FDR-corrected p < 0.01), with the latter two suggesting high energy metabolism and enhanced glycolysis in the gut lumen in response to alcohol. Consistent with the long-term alcohol exposure, mucosal damage and oxidative stress markers (N-acetylated amino acids, 2-hydroxybutyrate, and metabolites of the methionine cycle) increased in L vs. S and C (FDR-corrected p < 0.01). Overall, S showed few differences vs. C, possibly due to the long-term, chronic alcohol exposure needed to alter the normal gut microbiota. In the three groups, the fecal microbiome barely differed between conditions D and A, whereas the metabolome shifted in the transition from condition D to A. In conclusion, changes in the fecal microbiome and metabolome occur after significant long-term excessive drinking and are only partially affected by acute forced abstinence from alcohol. These results provide novel information on the relationship between the fecal microbiome and metabolome in a controlled experimental setting and using a unique non-human primate model of chronic excessive alcohol drinking.},

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A relationship between the gut microbiome and alcohol use disorder has been suggested. Excessive alcohol use produces changes in the fecal microbiome and metabolome in both rodents and humans. Yet, these changes can be observed only in a subgroup of the studied populations, and reversal does not always occur after abstinence. We aimed to analyze fecal microbial composition and function in a translationally relevant baboon model of chronic heavy drinking that also meets binge criteria (drinking too much, too fast, and too often), i.e., alcohol ~1 g/kg and blood alcohol levels (BALs) ≥ 0.08 g/dL in a 2-hour period, daily, for years. We compared three groups of male baboons (Papio anubis): L = Long-term alcohol drinking group (12.1 years); S = Short-term alcohol drinking group (2.7 years); and C = Control group, drinking a non-alcoholic reinforcer (Tang®) (8.2 years). Fecal collection took place during 3 days of Drinking (D), followed by a short period (3 days) of Abstinence (A). Fecal microbial alpha- and beta-diversity were significantly lower in L vs. S and C (p's < 0.05). Members of the commensal families Lachnospiraceae and Prevotellaceae showed a relative decrease, whereas the opportunistic pathogen Streptococcus genus showed a relative increase in L vs. S and C (p's < 0.05). Microbiota-related metabolites of aromatic amino acids, tricarboxylic acid cycle, and pentose increased in L vs. S and C (FDR-corrected p < 0.01), with the latter two suggesting high energy metabolism and enhanced glycolysis in the gut lumen in response to alcohol. Consistent with the long-term alcohol exposure, mucosal damage and oxidative stress markers (N-acetylated amino acids, 2-hydroxybutyrate, and metabolites of the methionine cycle) increased in L vs. S and C (FDR-corrected p < 0.01). Overall, S showed few differences vs. C, possibly due to the long-term, chronic alcohol exposure needed to alter the normal gut microbiota. In the three groups, the fecal microbiome barely differed between conditions D and A, whereas the metabolome shifted in the transition from condition D to A. In conclusion, changes in the fecal microbiome and metabolome occur after significant long-term excessive drinking and are only partially affected by acute forced abstinence from alcohol. These results provide novel information on the relationship between the fecal microbiome and metabolome in a controlled experimental setting and using a unique non-human primate model of chronic excessive alcohol drinking.