Functional genetic signatures of the gut microbiome in cardiometabolic diseases: mechanisms and translational opportunities.

The human gut microbiome plays a very important role in the regulation of host metabolism and overall physiological homeostasis. Disruptions in microbial community function have been increasingly implicated in cardiometabolic diseases, including obesity, type 2 diabetes, cardiovascular disease, and metabolic dysfunction-associated liver disease. Advances in metagenomic sequencing have identified functional genetic signatures within the gut microbiome for short-chain fatty acid biosynthesis, bile acid metabolism, lipopolysaccharide (LPS) production, amino acid metabolism, trimethylamine N-oxide (TMAO) generation, and carbohydrate-active enzymes (CAZymes). Across cardiometabolic conditions, a consistent pattern emerges of depletion of beneficial metabolic functions and enrichment of pro-inflammatory and metabolically disruptive pathways. These findings point to the importance of microbial functional capacity, rather than taxonomic composition alone, in shaping disease risk and progression. This review explores the functional genetic signatures for cardiometabolic diseases and translational potential of these signatures including their potential roles as diagnostic biomarkers, therapeutic targets, and tools for precision therapy. This understanding of microbiome-derived functional pathways may inform the development of targeted strategies aimed at restoring metabolic balance and improving cardiometabolic health.