Research Profile

This project focuses on examining the potential role of gut microbiome and blood metabolites in the progression of gestational diabetes mellitus (GDM) to type 2 diabetes (T2DM). While it is widely recognized that GDM substantially increases the lifetime risk of T2DM, the mechanism remains incompletely understood. Existing epidemiological studies have shown the promise of utilizing gut microbiome and metabolomics in revealing potential biomarkers and pathways associated with GDM and T2DM; however, few studies have investigated their roles in the GDM-to-T2DM transition. To address this important research gap, we will perform an integrated microbiome-metabolomics analysis of GDM with T2DM risk within a U.S. Hispanic/Latino population, and validate in an external U.S. population (mostly White participants) to extend the generalizability of our findings. This study will enhance our understanding of the molecular signatures underlying the GDM-to-T2DM transition. More importantly, given the modifiable nature of the gut microbiome, identification of bacterial taxa, functions, and related metabolites linking GDM to incident T2DM will facilitate the development of novel preventive and therapeutic targets/pathways against GDM-related T2DM, thereby informing effective prevention strategies and tailored interventions.

The primary purpose of our project is to help inform strategies to reduce the risk of T2DM in women with a history of GDM. Based on existing evidence, we hypothesize that women with history of GDM exhibit an unfavorable gut bacterial profile, potentially associated with an unfavorable metabolite profile, and an increased risk of developing T2DM. Thus, we will identify key gut microbiota and related metabolic signatures implicated in the GDM-to-T2DM transition. Our findings may contribute knowledge to GDM management and later-life T2DM prevention in the following aspects: 1) the molecular markers uncovered through our research may assist clinicians in early identification of women who are at higher risk for developing T2DM, which is critical for timely clinical management of T2DM; 2) our findings can provide actionable insights into potential microbial targets that can guide prevention/intervention strategies and mitigate T2DM risk in women with a history of GDM. Such targeted approaches may facilitate personalized care and risk reduction.

Through my academic training and research experience in epidemiology, I have developed a broad background and a strong interest in the intersection of maternal health, gestational diabetes, gut microbiome, and metabolomics/lipidomics. During my PhD training, I gained tremendous experience in running a large-scale birth cohort. In a GDM nested case-control design within the birth cohort, I led and collaborated on various omics/biomarkers research projects, aiming to identify the molecular signatures for GDM prediction and unravel the mechanisms of pathogenesis. Currently, I am undergoing my postdoctoral training, a phase that has further refined my skills in multi-omics data analysis. My research training and experience have motivated me to expand my prior work to multi-omics research in the GDM-to-T2DM transition, which also aligns with my aspiration to specialize and make deeper contributions specifically within the GDM research field. This award will provide a unique opportunity to extend my prior research, and help me master the necessary skills and gain important clinical insights in the following areas: (i) programming and bioinformatics in gut microbiome and metabolomics data analysis; (ii) GDM and T2DM systems biology; (iii) clinical knowledge of GDM management; and (iv) grant development and collaboration skills. This award will prepare me to become an independent investigator in multidisciplinary GDM research.

The fact that not all women with a history of GDM will develop T2DM in their later life suggests an unexplained heterogeneity in GDM-related T2DM risk. With the rapid advancements in ‘omics’ technologies, including human genomics, transcriptomics, epigenomics, metabolomics, proteomics, and metagenomics, ‘omics’ signatures have shown great potential in elucidating mechanisms and identifying high-risk populations in large-scale epidemiological studies. The integration of advanced multi-omics technologies with clinical data holds the promise to pave the way for precision medicine in GDM and GDM-related T2DM, as well as other GDM-related cardiometabolic diseases. Furthermore, given the close interplay between gut microbiota and glucose homeostasis, it becomes particularly promising to explore and validate how gut bacteria influence metabolism and contribute to T2DM risk in women with a history of GDM, which may unveil novel targets for the prevention and intervention of T2DM.