Multi-Omics Analysis of Bariatric Surgery's Impact on Type 2 Diabetes and Prediabetes

Bariatric surgery is a promising intervention for managing obesity-related metabolic disorders; however, its effects on cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D) remain poorly understood. To address this gap, we utilized a multi-omics approach to investigate how bariatric surgery influences Emirati individuals with T2D and prediabetes, focusing on the early detection of CVD markers. We longitudinally profiled 19 patients over a 9-month period, collecting omics data, including whole-genome sequencing (WGS), protein immunoassays, untargeted metabolomics, and 16S rRNA sequencing to determine gut microbiome composition. Through this study, we showed that bariatric surgery reduced CVD risk and inflammatory biomarkers while inducing changes in the gut microbiome and metabolomic profiles. We identified four inflammatory biomarkers (FGF-basic, TNFSF13, IL-8, and IL-1Ra) that were significantly altered following surgery (p < 0.05). Additionally, we identified 98 metabolites that showed significant changes after surgery that are involved in folate biosynthesis, glycerophospholipid, and retinol metabolism. Eighteen microbial genera were found to differentiate between the pre- and post-surgery states. Our analysis revealed four microbial genera (Enterobacter, Enterococcus, Gemella, and Erysipelotrichaceae UCG-003) associated with two T2D SNPs (rs11830243 and rs6978118) and three CVD SNPs (rs9490306, 62207434, and rs34606058). These genera formed the network's central hub, connecting host genetic variants, metabolic pathways, and clinical data, highlighting their role in host-microbiome interactions. The study quantifies the impact of phenotypic factors on CVD progression among UAE nationals, contributing to a deeper understanding of cardiometabolic health within this population.