Gut microbiota- and probiotic-derived bioactive metabolites: mechanisms, evidence, and therapeutic potential in metabolic disorders.

The gut microbiota is a taxonomically, genetically, and metabolically diverse and dynamic community of different microbial groups, including bacteria, archaea, fungi, and viruses, which are either in mutualistic or commensal relationships with their host, performing important metabolic regulation functions that bring a range of health benefits through the action of a wide range of bioactive compounds. These include short-chain fatty acids, secondary bile acids, exopolysaccharides, conjugated linoleic acids, tryptophan and indole derivatives, bacteriocins and antimicrobial peptides, and vitamins. Their health benefits include intestinal epithelial integrity, immunomodulation, metabolism, energy homeostasis, and host-gut microbiome interactions. A shift in the compositional and functional balance of the gut microbiota has been strongly linked to various metabolic disorders, including obesity, type 2 diabetes mellitus, metabolic syndrome, and non-alcoholic fatty liver disease. The use of these probiotic-derived metabolites as an alternative or complement to standard therapeutic procedures is gaining traction within the scientific community because of potential benefits such as improved stability, standardized dosing, minimal risks of genetic mutability through gene transfer, and pathogenicity. In this narrative review, we searched popular databases such as PubMed and Google Scholar for relevant materials, with emphasis on quality and rigor. This review discusses the current state of knowledge concerning the principal groups of gut microbiota- and probiotic-derived metabolites, their biosynthetic pathways, mechanisms of action, and origin. It presents a synthesized knowledge of the potential therapeutic benefits of these bioactive molecules in metabolic disorders. An attempt is made to critically evaluate their therapeutic benefits from available evidence. The review presents an interspersed discussion of the key constraints limiting the applicability of these metabolites in clinical metabolic therapy. It ends by highlighting key future research areas necessary for the eventual applicability of these metabolites as effective agents against metabolic diseases.