Abstract 074: Interplays of ADH1B Genotype, Alcohol Consumption, and Gut Microbiota in Relation to Insulin Resistance

Background: Alcohol consumption has been linked to alterations in gut microbiota and insulin resistance. The alcohol dehydrogenase 1B ( ADH1B) gene plays a crucial role in alcohol catabolism, where rs1229984 variant carriers (CT/TT) catabolize ethanol at an 80-fold faster rate than non-carriers (CC). Methods: We analyzed fecal metagenomic sequencing data from diabetes-free participants in the Hispanic Community Health Study/Study of Latinos. We used ANCOMBC to identify gut microbiota associated with alcohol consumption in non-carriers (n=1,399) and carriers (n=193). We constructed genotype-specific gut microbiome scores (GMSs) based on identified species associated with alcohol consumption to examine how microbiota may influence the relationship between alcohol consumption and insulin resistance in non-carriers and carriers. Insulin resistance was defined as HOMA-IR > 2.5. Results: Higher alcohol consumption was associated with lower odds of insulin resistance in non-carriers. Distinct microbial species associated with alcohol consumption were identified in non-carriers (54 species) and carriers (16 species) ( Fig A ). In non-carriers, the genotype-specific GMS modified the relationship between alcohol consumption and insulin resistance (P interaction =0.011). The odds ratios (OR) for insulin resistance with increasing alcohol consumption levels across low, moderate, and high tertiles of GMS were 0.75 (95%CI 0.58-0.96), 0.82 (0.67-1), and 1.13 (0.93-1.39), respectively ( Fig B ). We identified that abundance of individual alcohol-related species in non-carriers, such as Prevotella copri (enriched with alcohol consumption) , Ruminococcus callidus (enriched) , and Erysipelatoclostridium ramosum (depleted) , modified the relationship between alcohol consumption and insulin resistance in non-carriers ( Fig C ). Conclusions: Our findings suggest a potential role of gut microbiota in the protective association between alcohol consumption and insulin resistance in ADH1B variant non-carriers.