Blood proteomic signatures of diabetes and gut dysbiosis - Summary/Abstract The Hispanic/Latino population, one of the fastest growing segments in the US, is disproportionately affected by type 2 diabetes (T2D), but the underlying mechanisms are largely unknown. There is an urgent need to better understand this phenomenon thus to develop more effective approaches for T2D prevention and treatment in this population group. Technological advances offer new opportunities for deciphering novel signatures of T2D, potentially improving our understanding of pathogenesis and discovery of novel targets to prevent and treat T2D. Applying emerging omics approaches, recent studies have identified many circulating proteins and related biological pathways associated with risk of T2D. However, proteomics data on risk of T2D is sparse in US Hispanics. Differences in the protein-T2D associations across populations observed in previous studies and our preliminary analysis further emphasizes the necessity to conduct proteomic study of T2D in different population groups. Moreover, emerging evidence suggested that the gut microbiota may play an important role in human chronic diseases including T2D through regulating host metabolism and inflammation/immune activation pathways, but few studies have integrated proteomics with microbiome data to investigate the relationship between gut dysbiosis (i.e., unfavorable alteration in the gut microbiota) and T2D and underlying biological mechanisms. To address these knowledge gaps, we propose to profile plasma proteome (5000+ proteins by Olink Explore HT) in 2,300 individuals free of diabetes (including repeated proteome measures in 1000 individuals over ~6 years)) from the Hispanic Community Health Study/Study of Latinos (SOL), an on-going prospective cohort with extensive data on multi-omics, sociocultural and behavioral factors, as well as multiple repeated glycemic traits (including insulin resistance and secretion measures from oral glucose tolerance test) and incident T2D during follow-up. Our overarching goal is to identify blood proteomic signatures, and their biological pathways related to genetic and environmental factors (e.g., gut microbiome) for the development of T2D in US Hispanics. Moreover, we will also use existing data from other cohorts including Hispanic, White, Black and Asian participants to validate, compare and generalized our findings across different populations. Findings from this project will advance our understanding of T2D etiology and provide new insights into T2D prevention and treatment in US Hispanics and other populations.
