Microbe-associated metabolites (MAMs)

Microbe-associated metabolites (MAMs) represent a vast and heterogeneous class of small molecules produced, modified, or degraded by the commensal microbiota, particularly those residing in the human gastrointestinal tract [1, 2]. These molecules act as quintessential signaling intermediaries in inter-kingdom communication, exerting profound effects on host physiology both locally in the gut and systemically in distant organs like the liver, brain, and heart [11, 13, 20]. Common examples include short-chain fatty acids (SCFAs), which modulate immune function and metabolism through G protein-coupled receptors (GPCRs), and secondary bile acids that activate nuclear receptors such as FXR to regulate lipid and glucose homeostasis [2, 10, 11]. Dysregulation of MAM profiles is strongly linked to the pathogenesis of various chronic conditions, including cardiovascular disease, metabolic syndrome, inflammatory bowel disease (IBD), and colorectal cancer [1, 3, 5, 14]. For instance, elevated levels of trimethylamine N-oxide (TMAO) have been causally linked to atherosclerosis and renal failure, making the microbial enzymes responsible for its production attractive drug targets [1, 18]. Therapeutic strategies currently include the direct administration of beneficial metabolites as postbiotics, the use of small-molecule inhibitors to block microbial biosynthetic enzymes, and the targeting of host receptors that sense these metabolites [1, 2, 20].

Other names

Microbial metabolitesMicrobiota-derived metabolitesSpecialized microbial metabolitesPostbioticsMicrobiome-associated metabolites

Therapeutic intervention involves direct administration of beneficial metabolites (postbiotics), modulation of metabolite production through the inhibition of specific microbial enzymes (e.g., TMA lyase), sequestration of harmful metabolites using binding agents, or the pharmacological activation/antagonism of host receptors such as G protein-coupled receptors (GPCRs) and nuclear receptors like FXR and TGR5 [1, 2, 10, 11, 20].