Longitudinal Changes in the Oral and Gut Microbiome of Individuals with Alcohol Dependence

Clinical Center

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Abstract

We hypothesized that abnormalities in the oral/gut microbiome will be detectable on admission, and that these will also renormalize with abstinence and resumption of ordinary diet and oral hygiene. If not, the findings in this study could point to the need for other interventions, such as administration of probiotics. Twenty-three participants admitted to the Clinical Center for alcohol detoxification were enrolled. All patients were admitted under the Unit and Clinic Evaluation, Screening, Assessment, and Management protocol (14-AA-0181), which includes adults 18 years of age or older seeking inpatient treatment for alcohol use disorders (AUD). Oral (tongue brushings) and gut (stool) specimens were collected daily until the end of the first week, then once a week for up to 28 days. Demographic characteristics, detailed drinking and dietary histories, measures of addiction severity, comorbid mental disorders, and metabolic indicators of other disease were collected for correlation with microbiological results. Dietary records included use of probiotics. Exclusion criteria included use of antibiotics, corticosteroids or immunosuppressive agents within the past month. Informed consent was obtained after consent for the screening and treatment protocol (14-AA-0181) and in accordance with policies protecting participants with impaired decision-making. Microbial identification included 16S rRNA analysis and a validated Next Generation Sequencing analysis pipeline. Statistical comparisons between each patients oral and gut microbiome samples was evaluated and all results from this population will also be compared to published microbiomes in both healthy volunteers as well as existing data from alcohol dependent individuals. Participants were compensated for research-related discomfort and inconveniences in accordance with NIH guidelines. This study has finished accrual. Study remains open for further analysis using shotgun sequencing. Additional manuscripts have been published and/or are in preparation. A secondary analysis protocol (#000796) was IRB approved entitled 'Associations Between the Cytokine and Metabolite-Associated Gut Microbiome Bacteria, Structural MRI Features and Clinical Phenotype (craving, anxiety, and depression) in patients with AUD. Shotgun metagenomics sequencing of gut microbiome samples were performed on stored fecal specimens at the beginning of week 1, week 2, week 3 and week 4 under this protocol. Cross-sectional analysis of shotgun metagenomics data in association with MRI and clinical phenotype features is complete and these results were published in 2024. Longitudinal analysis of weekly gut microbiome community data in association with changes in symptom severity during inpatient treatment for AUD is ongoing and these results are being compiled for publication.