Identification of key taxonomic and metabolic players in the gut metagenome of T2D Patients

Abstract

Despite advancements in diagnostic and treatment approaches, Type 2 Diabetes is a pervasive metabolic disorder with significant global health implications The potential impact of the gut metagenome on human health and disease outcomes, including diabetes, has been uncovered by recent advancements in metagenomic analysis. Emerging evidence suggests that alterations in the composition and functions of gut bacterial taxa may contribute to the development and progression of type 2 diabetes. Additionally, carbohydrate active enzymes produced by gut microbial communities have shown impact on type 2 diabetes. However, the specific mechanisms of these carbohydrate active enzymes to type 2 diabetes are not well understood. This study investigates the gut metagenome role in type 2 diabetes, focusing on key taxonomic and metabolic players and their interactions with glucose-lowering drugs such as metformin and acarbose. Utilizing advanced metagenomic analyses and machine learning models, the study identifies key microbial taxa and carbohydrate active enzyme protein families associated with type 2 diabetes. Key findings include the identification of specific microbial taxa linked to improved glycemic control and potential metabolic pathways that could be targeted for therapeutic interventions. The research highlights the gut metagenome and carbohydrate active enzymes of microbial communities’ potential as a modifiable factor in type 2 diabetes management. Notable results include a significant increase in the abundance of Romboutsia timonensis (p = 0.000003, q = 0.003) in low response and Bacteroides uniformis (p = 0.00003, q = 0.01) with the acarbose drug. The identified key carbohydrateactive enzyme protein families with low responses of acarbose are GH3, GH31, CE4, and xiv GH2 (p = 0.001, q = 0.006, p = 0.002, q = 0.01, p = 0.001, q = 0.006, and p = 0.005, q = 0.02 respectively). This study explores the key players of gut metagenome and novel associations of carbohydrate-active enzyme protein families with T2D, suggesting a direct link between key metagenome, carbohydrate-active enzyme families, and T2D outcomes.