Ethanol is a common substance of misuse and abuse, addiction is rampant globally, and chronic ethanol abuse affects multiple organs and physiological systems, including: the hepatic, renal, neurological, cardiovascular, hematologic, and immune systems. There is increasing awareness that the gut microbiota, a 'forgotten' organ system, not only affects the majority of human physiologic systems but also participates in ethanol metabolism and is affected by ethanol consumption. Two recent studies support that there are dramatic and consistent shifts in gut microbial communities in laboratory mice exposed to ethanol and in people that ingest copious amounts of ethanolic beverages versus people that abstain from drinking ethanol. Thus, the gut microbiota is an 'organ' system that merits more comprehensive biomedical study in response to ethanol exposure. Advances in sequencing technology and their analysis pipelines have enabled rapid and low cost surveys of gut microbial communities. While fecal surveys performed in the context of ethanol exposure provide important descriptive knowledge about the composition of a gut microbial, such studies do not provide direct information about how the gut microbiota participate in ethanol metabolism nor do such studies furnish a nuanced understanding of how ethanol exposure affects a gut microbiota. Our over-arching hypothesis is that the gut microbiota play a fundamental role in ethanol metabolism. We also hypothesize the following: (i) specific and identifiable members of the gut microbiota utilize ethanol as a carbon source, (ii) chronic ethanol consumption causes increase oxygen availability in the gut which drives changes in gut microbial community composition, and (iii) the microbiota perform metabolic transformations of ethanol distinct from the host. It is our hope that generating a mechanistic understanding of how members of the gut microbiota metabolize ethanol and are directly affected by ethanol and its metabolism in the colon will provide opportunities to reduce and ameliorate the toxicities of chronic ethanol exposure for human physiology.

Public Health Relevance

Ethanol is a common substance of abuse and its chronic abuse is a major public health problem. We aim to gain a deeper understanding of the role of the gut microbiota in ethanol metabolism with the goal to reduce the toxicities of chronic ethanol exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AA023207-02
Application #
9031015
Study Section
Neuroscience Review Subcommittee (AA)
Program Officer
Gao, Peter
Project Start
2015-03-10
Project End
2017-02-28
Budget Start
2016-03-01
Budget End
2017-02-28
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code