Gut microbiota-derived metabolites and their immunomodulatory roles

Metabolite typeImmunomodulating propertyAssociated diseasesReferences
Metabolic end products
Short-chain fatty acids (SCFAs)Support gut barrier integrity, reduce pro-inflammatory cytokines, promote Treg differentiation, neutrophil migration, and B cell class switchingMetabolic syndrome, cardiovascular disease, inflammatory bowel disease, colorectal cancer, and chronic kidney disease[1924]
Tryptophan and indole derivativesRegulate gut barrier, motility, and hormone secretion; modulate immune responses via AhR receptor, promoting immune toleranceInflammatory bowel disease, irritable bowel syndrome, obesity, colorectal cancer[18, 23, 25, 26]
De novo products
Branched-chain amino acids (BCAAs)Crucial for protein synthesis, cell growth, and energy metabolismType 2 diabetes, obesity, cardiovascular disease, colorectal cancer[17, 23, 27, 28]
Polyamines (PAs)Maintain intestinal barrier, reduce oxidative stress, inhibit inflammatory cytokine productionColorectal cancer, other tumors[23, 2931]
Bacterial-derived vitaminsSupport metabolic processes, regulate DNA synthesis, energy metabolism, immune cell functionCardiovascular disease[18, 32, 33]
Modified host metabolites
Secondary bile acids (BAs)Modulate activity of innate immune cells (macrophages, dendritic cells), regulate lipid and glucose metabolismMetabolic dysfunction-associated steatotic liver disease, inflammatory bowel disease, colorectal cancer[18, 3436]

AhR: aryl hydrocarbon receptor; Tregs: regulatory T cells