Deciphering the molecular complexity of dyslipidemia : multi-omics meta-analysis of the gut microbiome and the host physiology

Abstract

The gut microbiome is intricately linked with various aspects of health and physiology, serving as both a potential diagnostic marker and therapeutic target. Understanding its mechanistic in􀏐luences on systemic processes, particularly those affecting remote organs, is crucial. One key research area is the gut microbiome's interaction with the cardiometabolic system, particularly dyslipidemia. Dyslipidemia, characterized by abnormal levels of lipids in the blood, is a major risk factor for cardiovascular disease, Type II Diabetes, obesity, and metabolic syndrome. These conditions are characterized by disturbances in glucose metabolism, lipid metabolism, and blood pressure regulation, often leading to severe complications like heart attacks, strokes, Non-alcoholic fatty liver disease (NAFLD), and chronic kidney diseases. Alterations in the gut microbiome are associated with dyslipidemia. Speci􀏐ic gut microbiome-derived metabolic products have been linked causatively to the onset or delay of these disorders. Despite this, our understanding remains incomplete, lacking a comprehensive catalogue of the microbiome-metabolite network-host-pathway links. This study adopts a data-driven, multi-level analysis of human-derived gut microbiome and host metabolome datasets to investigate these connections. We performed a three-level interaction investigation: 􀏐irst, identifying gut-microbiome-associated serum metabolites linked with dyslipidemia health markers; second, deciphering links between the gut microbiome and serum metabolome; and third, validating these 􀏐indings by associating speci􀏐ic gut microbial community members with dyslipidemia markers. To achieve this, we utilized 17 large, publicly available paired datasets, including gut microbiome and metabolome data, host metabolome and dyslipidemia marker pro􀏐iles, and gut microbiome and host dyslipidemia marker pro􀏐iles. This comprehensive approach has the potential to enhance our understanding of the gut microbiome's role in systemic health and dyslipidemia.