Abstract P518: Distinctive Blood Metabolomic Profiles Between US-Born and Foreign-Born Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Introduction:US-born Hispanics have a worse cardiometabolic profile compared to foreign-born Hispanics, but the underlying mechanisms are not fully understood.Hypothesis:We hypothesize that, compared to foreign-born Hispanics, US-born Hispanics have a distinctive blood metabolomic profile, which might be related to diet/lifestyle and gut microbiota and associated with health outcomes.Methods:Serum levels of 634 metabolites were profiled in US Hispanics in the Hispanic Community Health Study/Study of Latinos (N=3941 in discovery dataset; N=2368 in replication dataset). We used multiple linear regression to identify metabolites associated with US nativity. Machine-learning algorithms were used to identify potential determinants of metabolites based on genetics, sociodemographic factors, diet, lifestyle, clinical parameters, and gut microbiota. We examined prospective associations of baseline metabolites with risk of incident diseases during a 6-year follow-up using Poisson regression.Results:We identified 158 metabolites associated with US nativity in discovery dataset (FDR<0.05), 135 of which were validated in replication dataset (87 higher and 48 lower in US born vs foreign-born). A metabolomic score showed a high discriminatory ability for US-born vs foreign-born Hispanics (AUC = 0.84 and 0.82 in discovery and replication datasets, respectively) and a dose-response relationship with longer duration of US residence. Variations of these US-nativity related metabolites were explained more by nongenetic factors, especially diet and gut microbiota, compared to those unrelated to US nativity, while variations explained by genetics between these two groups of metabolites were similar. Specifically, the US-born related metabolomic profile was characterized by lower levels of many metabolites in amino acid and xenobiotic pathways (e.g., ergothioneine, phenylpropionate, indole propionate, β-cryptoxanthin, carotene diol). These metabolites were positively associated with plant-based food intake (e.g., whole grain, fruits, vegetables) and beneficial fiber-utilizing bacteria (e.g., Eubacterium, Roseburia, Oscillibacter).Cardiometabolic and kidney function traits showed stronger overall associations with US-nativity related metabolites compared to other clinical traits (e.g., liver function, lung function). Prospective analyses showed that metabolites higher in US-born Hispanics were generally associated with higher risk of server obesity, hypertension, diabetes, chronic kidney disease and asthma, while those higher in foreign-born Hispanics were generally associated with lower risk of these diseases.Conclusion:Compared to foreign-born Hispanics, US-born Hispanics showed an unfavorable blood metabolomic profile associated with multiple chronic diseases, which might be partially related to diet and gut microbiota acculturation.