(LB03-24-26) Exercise Minimally Impacts Alcohol-Associated Gut Dysbiosis Yet Reveals a Microbial Association With Alcohol-Associated Muscle Disease Phenotype.

Objectives: Alcohol disrupts the gut microbiome leading to gut leakiness and the release of inflammatory mediators. Alcohol use is also associated with muscle atrophy, weakness and poor metabolic performance and emerging data have implicated alcohol-induced gut dysbiosis as a contributing cause. Recently, we showed that daily exercise offsets some aspects of alcohol- associated muscle disease (AAMD), while others have reported the gut microbiome is responsive to exercise. Therefore, the objective of this study was to determine whether exercise could offset the negative impact of chronic alcohol use on the gut microbiome.

Methods: 12-week-old female C57BL6/Hsd mice were randomized into 4 groups: control-sedentary (CON-SED), control-exercise (CON-EX), alcohol-sedentary (ETOH-SED), or alcohol-exercise (ETOH-EX). Lieber Decarli liquid diet was used to deliver alcohol (ETOH). Exercise groups had access to a voluntary running wheel for 2h/day. Fecal matter collected at the end of the 6-week intervention was sequenced for microbial composition.

Results: Microbial structure assessed by Bray-Curtis dissimilarity demonstrated a significant effect of alcohol regardless of exercise (CON-EX vs ETOH-EX, p=.002) (CON-SED vs ETOH-SED, p=.0001). Alpha diversity (via Shannon and Chao1 indexes) was lower in ETOH-SED vs. CON-SED and CON-EX) with exercise slightly offsetting this ETOH effect. Changes at the genus level were assessed to identify potential microbial mediators. Notably, Romboutsia showed the largest difference in relative abundance when comparing effect size in both CON-SED vs ETOH-SED and CON-EX vs ETOH-EX. Furthermore, in ETOH groups, the increase in Romboutsia was negatively correlated with grip strength, lean mass and the mass of several muscles, representing key features of AAMD.

Conclusions: Alcohol consumption altered gut microbiome structure and diversity. Exercise showed changes at the genus level amongst treatment groups, whereby Romboutsia displayed a negative correlation with grip strength within ETOH providing evidence of alcohol’s effect on the gut-muscle axis. Further research should explore whether Romboutsia is a potential nutritional target to prevent or attenuate AAMD.

Funding Sources: American College of Sports Medicine Grant to A. Tice; FSU start-up funds to JLS.