Longitudinal gut microbiome changes in alcohol use disorder are influenced by abstinence and drinking quantity

ABSTRACT

Many patients with alcohol use disorder (AUD) consume alcohol chronically and in large amounts that alter intestinal microbiota, damage the gastrointestinal tract, and thereby injure other organs via malabsorption and intestinal inflammation. We hypothesized that alcohol consumption and subsequent abstinence would change the gut microbiome in adults admitted to a treatment program. Stool and oral specimens, diet data, gastrointestinal assessment scores, anxiety, depression measures and drinking amounts were collected longitudinally for up to 4 weeks in 22 newly abstinent inpatients with AUD who were dichotomized as less heavy drinkers (LHD, <10 drinks/d) and very heavy drinkers (VHD, 10 or more drinks/d). Next-generation 16 S rRNA gene sequencing was performed to measure the gut and oral microbiome at up to ten time points/subject and LHD and VHD were compared for change in principal components, Shannon diversity index and specific genera. The first three principal components explained 46.7% of the variance in gut microbiome diversity across time and all study subjects, indicating the change in gut microbiome following abstinence. The first time point was an outlier in three-dimensional principal component space versus all other time points. The gut microbiota in LHD and VHD were significantly dissimilar in change from day 1 to day 5 (p = .03) and from day 1 to week 3 (p = .02). The VHD drinking group displayed greater change from baseline. The Shannon diversity index of the gut microbiome changed significantly during abstinence in five participants. In both groups, the Shannon diversity was lower in the oral microbiome than gut. Ten total genera were shared between oral and stool in the AUD participants. These data were compared with healthy controls from the Human Microbiome Project to investigate the concept of a core microbiome. Rapid changes in gut microbiome following abstinence from alcohol suggest resilience of the gut microbiome in AUD and reflects the benefits of refraining from the highest levels of alcohol and potential benefits of abstinence.

KEYWORDS:

• Gut microbiome
• molecular methods
• alcohol use disorder
• oral microbiome
• substance use

Disclosure of potential conflicts of interest

The authors have declared no conflicts of interest.

Acknowledgements

We would like to thank the nurses, physicians and other research staff who assisted with this study on the 1 Southeast Unit at the Clinical Center, NIH, and the staff of the National Institute of Dental and Craniofacial Research dental clinic. Additionally, we greatly appreciate all the patients who participated for their time and dedication in completing the study.

Authors Contributions

Nancy Ames – principal investigator, designed the protocol, collected specimens, analyzed the data and wrote the manuscript. Co-first author.

Jennifer Barb – Assisted with the design of the protocol analyzed the microbiome specimens. Developed the pipeline and RMS processes. Wrote major sections of the manuscript. Co-first author.

Kornel Schuebel – assisted with study design and supervised/and or performed all laboratory procedures.

Sarah Mudra – assisted with study design; performed the majority of the lab work, analyzed specimens, edited the manuscript.

Brianna Meeks: analyzed data, assisted with sequencing, contributed to the writing and editing of the manuscript.

Kelly Ratteree and Shanna Bernstein – collected and analyzed dietary data, edited manuscript.

Gwenyth Wallen – collaborated on the conceptualization of the original research aims and study design, provided revisions to the manuscript.

Ralph Tuason – collected specimens analyzed data and provided revisions to the manuscript.

Nancy Diazgranados – assisted with the design of the protocol, provided expertise regarding AUD and consulted on the manuscript.

Narjis Kazmi – edited the manuscript and analyzed data.

Alyssa Brooks – assisted with the design of the study. Collected data and revised manuscript.

Michael Krumlauf – assisted with the design of the study and collected specimens.

David Goldman – assisted with the design of the original protocol. Provided critical analysis of the manuscript and editing.

Data Availability

The microbiome sequencing data are available at the Sequencing Read Archive (SRA) at https://www.ncbi.nlm.nih.gov/sra/docs/. The accession number for the data is PRJNA575744. The oral sequencing data is available URL: https://www.ncbi.nlm.nih.gov/sra/PRJNA634528. The ascension number is PRJNA634528.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

Funds for this study were provided by the NIH Clinical Center intramural research funds and NIAAA Annual Report #Z01AA000280-18 .