Discrete interplay of gut microbiota L-tryptophan metabolites in host biology and disease

Mol Cell Biochem. 2023 Oct 20. doi: 10.1007/s11010-023-04867-0. Online ahead of print.ABSTRACTThe gut microbiota and the host maintain a conjoint relationship and together achieve optimal physiology via a multitude of interactive signalling cues. Dietary-derived L-tryptophan (L-trp) is enzymatically metabolized by the resident symbiotic gut microbiota to indole and various indole derivatives. Indole and indole metabolites secreted by the gut bacteria act locally in the intestinal cells as well as distally and modulate tissue-specific functions which are beneficial to the host. Functions attributed to these microbial indole metabolites in the host include regulation of intestinal permeability, immunity and mucosal roles, inflammation, and insulin sensitivity. On the other hand, dysregulation of gut microbiota L-trp metabolism compromises the optimal availability of indole and indole metabolites and can induce the onset of metabolic disorders, inflammation, liver steatosis, and decrease gut barrier integrity. Gut dysbiosis is regarded as one of the prime reasons for this deregulated microbial-derived indole metabolites. A number of indole metabolites from the gut bacteria have been identified recently displaying variable affinity towards xenobiotic nuclear receptors. Microbial metabolite mimicry concept can be used to design and develop novel indole-moiety-containing compounds with higher affinity towards the receptors and efficacy in preclinical studies. Such compounds may ser...
Source: Molecular and Cellular Biochemistry - Category: Biochemistry Authors: Source Type: research