TY - JOUR
T1 - Gut microbiome and metabolome in a non-human primate model of chronic excessive alcohol drinking
AU - Piacentino, Daria
AU - Grant-Beurmann, Silvia
AU - Vizioli, Carlotta
AU - Li, Xiaobai
AU - Moore, Catherine F.
AU - Ruiz-Rodado, Victor
AU - Lee, Mary R.
AU - Joseph, Paule V.
AU - Fraser, Claire M.
AU - Weerts, Elise M.
AU - Leggio, Lorenzo
N1 - Funding Information:
(DP); (D) NIH/NIAAA R01-AA15971 (PI: Elise Weerts, Ph.D., Johns Hopkins University) (CFM, EMW); (E) the Dean’s Endowed Professorship to Claire M. Fraser, PhD (University of Maryland School of Medicine) (SGB, CMF); (F) National Institutes of Health (NIH) Intramural Research Program (IRP) funding for the Section on Sensory Science and Metabolism (PI: Paule Joseph, Ph.D., C.R.N.P., NIH IRP), jointly supported by the NIAAA DICBR and the National Institute of Nursing Research Division of Intramural Research (CV, PVJ); (G) the Office of Workforce Diversity, National Institutes of Health Distinguished Scholar (PVJ); (H) the Rockefeller University Heilbrunn Nurse Scholar Award (PVJ); and (I) NIH IRP funding from the National Cancer Institute (VRR). Open Access funding provided by the National Institutes of Health (NIH).
Funding Information:
This study was supported by (A) National Institutes of Health (NIH) Intramural Research Program (IRP) funding ZIA-DA000635 and ZIA-AA000218 (Clinical Psycho-neuroendocrinology and Neuropsychopharmacology Section; PI: Lorenzo Leggio, M. D., Ph.D., NIH IRP), jointly supported by the NIDA IRP and the NIAAA Division of Intramural Clinical and Biological Research (DICBR) (DP, XL, MRL, LL), (B) Peter G. Dodge Foundation (PGDF) funding (Exploring Gut-Brain and Brain-Gut Interactions in Alcohol Use Disorder via Microbiota Investigations: A Pilot Study; PI: Lorenzo Leggio, M.D., Ph.D., NIH IRP) (DP, XL, MRL, LL), (C) Center on Compulsive Behaviors funding, NIH IRP via the NIH Director’s Challenge Award to Daria Piacentino, M.D., Ph.D., M.Sc.
Publisher Copyright:
© 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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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U2 - 10.1038/s41398-021-01728-6
DO - 10.1038/s41398-021-01728-6
M3 - Article
C2 - 34853299
AN - SCOPUS:85120627191
SN - 2158-3188
VL - 11
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 609
ER -