Signaling Metabolites in the Gut Microbiota-Organ Axes

The gut microbiome is positioned at the center of a hub that contributes to both the physiology and pathology of multiple distant organs. It does this by releasing beneficial signaling molecules that are synthesized by various microbial species. Beneficial metabolites that cross from the gut lumen into the circulation include the short-chain fatty acids (SCFAs), a range of tryptophan metabolites (TRPMs), the major polyamines, and certain secondary bile acids. The SCFAs act on G-protein-coupled receptors (GPRs) and on histone deacetylases (HDACs) and, in so doing, suppress inflammation. Tryptophan metabolites act mainly through the nuclear receptor AhR, enhancing gut barrier and blood-brain barrier integrity. The polyamines stabilize nucleic acids and regulate cell proliferation. The secondary bile acids have varied effects on the liver, brain, and lung. In addition, the microbiome contributes to deleterious cometabolites, such as trimethylamine N-oxide, p-cresyl sulfate, and indoxyl sulfate. We predict that clinical laboratories in the future will assay patient samples for an amalgamation of beneficial and detrimental microbiota metabolites as biomarkers of both health and disease risk.