Abstract 57: Gut Microbiota, Blood Metabolites and Left Ventricular Diastolic Dysfunction in US Hispanics/Latinos

Background: Left ventricular diastolic dysfunction (LVDD) is a precursor of heart failure (HF), but its relationship with gut dysbiosis and microbial-related metabolites remains unclear. Hypothesis: Alerted gut microbiota composition is associated with LVDD and blood metabolites, which can be used as indicators of gut dysbiosis. Methods: This study included up to 1996 adults (mean age: 59.4 years; 67.1% female; 45.9% with prevalent LVDD) from the Hispanic Community Health Study / Study of Latinos with echocardiography assessments, gut microbiota (512 bacteria species), and blood metabolome (669 metabolites) data. Cross-sectional associations of gut bacteria with prevalent LVDD and metabolites, and prospective associations of microbial-associated metabolites with incident LVDD were assessed. Results: Seven bacterial species were associated with LVDD (FDR-q <0.1), with inverse associations found for Intestinimonas_massiliensis , Clostridium_phoceensis, and Bacteroide_coprocola , and positive associations for Gardnerella_vaginali , Acidaminococcus_fermentans, Pseudomonas_aeruginosa and Necropsobacter_massiliensis . A total of 220 metabolites were found to be associated with identified bacteria (FDR-q <0.1), with 46 associated with prevalent LVDD (FDR-q <0.1). Of note, 21 metabolites were associated with incident LVDD over a median 4.3 years of follow-up, including many known microbial metabolites (e.g., indolepropionate, 3b-hydroxy-5-cholenoic acid and glycohyocholate). The use of these metabolites significantly improved the prediction of incident LVDD, outperforming models only with traditional risk factors (AUC=0.73 vs. 0.70, p=0.001). Metabolite-based proxy association analyses revealed potential prospective associations between 3 gut bacteria species (e.g., I.massilliensis and C.phoceensis ) and incident LVDD. Conclusion: Our study found gut bacteria and bacteria-associated metabolites linked to LVDD, suggesting their potential roles in this preclinical HF entity.