Abstract 69: Dietary Fiber, Gut Microbiota, Circulating Metabolomics, and Risk of Diabetes in US Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Introduction: Emerging evidence suggesting diabetes -protective effects of dietary fiber intake. However, the underlying mechanisms are not fully understood. Hypothesis: We hypothesize that higher dietary fiber intake can alter gut microbial composition /functional capacity and host circulating metabolomic profile, which may contribute to lower risk of diabetes. Methods: We evaluated the associations of dietary fiber intake with gut microbiome (measured by shotgun metagenomic sequencing, n=2959) and serum metabolome (639 metabolites measured by untargeted metabolomic approach, n=6198) in the HCHS/SOL cohort. We further examined prospective associations of baseline fiber/microbial-associated metabolites with incident diabetes over 6-years follow-up. Results: We identified 39 bacterial genera associated with fiber intake, after adjustment for sociodemographic, behavioral, and clinical factors. 12 of these fiber-associated genera were related with diabetes (e.g. the fiber-associated Roseburia was inversely associated with diabetes, Fig.1A ). We identified 83 fiber-associated metabolites which were clustered into 13 modules in network, 7 of which were significantly associated with risk of diabetes ( Fig.1B ). Some of these diabetes-associated metabolite modules were also associated with fiber/diabetes-associated bacterial taxa ( Fig.1C ). In particular, indolepropionate module, and another module comprised of the pro-vitamins such as beta-cryptoxanthin, were positively associated with fiber (all P<0.001) and inversely associated with diabetes risk (RR [95% CI] = 0.78[0.69, 0.89] and 0.83[0.72, 0.94] respectively), and both associated with the fiber-degradation genera Butyrivibrio (P<0.001). Conclusion: Among US Hispanics/Latinos, higher fiber intake was associated with favorable profiles of gut microbiota and circulating metabolites for diabetes, suggesting a potential role of gut microbiota and related metabolites in the link between dietary fiber intake and risk of diabetes.