process

IDO pathway (tryptophan to niacin conversion, Kynurenine Pathway)

Trp metabolism through the KP in the gut is mediated by the rate-limiting enzyme IDO1 and leads to the production of kynurenine (Kyn) and downstream products such as quinolinic acid (QA), niacin, nicotinamide adenine dinucleotide, and kynurenic acid (Kna) (Cervenka et al., 2017, Kennedy et al., 2017). The key role of the gut microbiota in stimulating IDO1 activity has been clearly demonstrated, notably in germ-free and antibiotic-treated mice. KP end products are implicated in the regulation of a number of host biological processes involving neurotransmission, inflammation, and the immune response. Moreover, some metabolites appear to exert specific effects in the gut. This is the case for Kna, whose concentration increases gradually along the gastrointestinal tract. Kna exhibits mucosal protective and immunoregulatory effects, probably through its G protein-coupled receptor, GPR35, which is mostly expressed in epithelial and immune cells (Gao et al., 2018). Two other enzymes, Trp 2,3-dioxygenase (TDO) and IDO2, metabolize Trp to Kyn, but these enzymes are not expressed in the gut and are not discussed here. In addition, several intestinal bacteria encode enzymes homologous to those of the eukaryotic KP and are thus also able to produce Kyn and downstream metabolites such as 3-hydroxyanthranilic acid (Vujkovic-Cvijin et al., 2013), which has neurotoxic effects (O'Farrell and Harkin, 2017).

Ref:
Agus A, Planchais J, Sokol H. Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe. 2018 Jun 13;23(6):716-724. doi: 10.1016/j.chom.2018.05.003. PMID: 29902437.

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Added on Jun 13, 2022 by Barbara Van De Keer
Edited on Jan 8, 2023 by Barbara Van De Keer

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