Longitudinal Gut Microbiome Changes in Alcohol Use Disorder  Are Influenced by Abstinence and Drinking Quantity
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 four weeks in 22 newly abstinent inpatients with AUD who were dichotomized as Less Heavy Drinkers (LHD, <10 drinks/day) and Very Heavy Drinkers (VHD, 10 or more drinks /day).  Next generation 16S 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=0.03) and from day 1 to week 3 (p=0.02). 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 highest levels of alcohol and potential benefits of abstinence.  Contact: Jennifer Barb. This submission was powered by METAGENOTE (https://metagenote.niaid.nih.gov).