Gut Microbes Take It to the Next Level? First Insights Into Farnesoid X Receptor Agonists of Microbial Origin
Abstrakt
The intestinal microbiome and its metabolites contribute to host (patho)physiology through signaling via host bile salt receptors. To assess the overall chemical effects of the microbiome at the level of an entire animal, Quinn et al. conducted untargeted metabolome analysis of 29 different organs of germ-free and specific pathogen-free (SPF) mice.
Unique microbial and metabolome profiles were evident along the gastrointestinal (GI) tract. An elegant mass spectrometry informatics approach led to the identification of three novel bile salt conjugates that were present along the entire intestinal length of SPF mice only, with highest levels observed in the small intestine.
Specifically, N-amidates of cholic acid (CA) and either leucine (Leu-CA), phenylalanine (Phe-CA), or tyrosine (Tyr-CA) were identified and shown to be produced by specific strains of Clostridium bolteae. Administration of these new bile salt conjugates to mice resulted in changes in ileal and hepatic gene expression compatible with local activation of the bile salt receptor, farnesoid X receptor (FXR).
Mining of public databases resulted in spectral matches to the novel bile salt conjugates in GI tract/fecal samples of patients with Crohn's disease and in cystic fibrosis.