Microbial metabolites as emerging Biomodulators of host function and disease susceptibility

The gut microbiota is increasingly recognized as a metabolic descriptor that shapes host physiology through amino acid utilization and its metabolites. This review integrates the roles of proteolytic, tryptophan-utilizing, and glutamate-metabolizing bacteria with host nutrient-sensing pathways (GCN2/eIF2α-ATF4 and mTORC1), emphasizing their influence on metabolism, immunity, and neurobehavioral function. Particular attention is given to how microbial metabolites, including short-chain fatty acids, bile acids, and indole derivatives, interact with host signaling pathways and inform translational strategies, such as dietary modulation, prebiotics, probiotics, postbiotics, and emerging engineered microbiome-based interventions. By mapping microbial pathways to clinical endpoints, we outlined how dietary and microbiome-based interventions can reduce the risk of chronic diseases. This bench-to-bedside perspective underscores the therapeutic potential of gut metabolites in personalized nutrition and in precision medicine. This review provides an integrated mechanistic perspective linking amino acid–metabolizing microbial communities to host nutrient-sensing pathways that regulate metabolism and immunity. Microbial metabolites have been highlighted as modifiable regulators with clear relevance to personalized nutrition and precision medicine by directly connecting these molecular interactions to dietary, postbiotic, and emerging microbiome-based interventions.