Emerging effects of tryptophan pathway metabolites and intestinal microbiota on metabolism and intestinal function

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dc.contributor.authorHyland, Niall P.
dc.contributor.authorCavanaugh, Cassandre R.
dc.contributor.authorHornby, Pamela J.
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2022-02-07T14:30:02Z
dc.date.available2022-02-07T14:30:02Z
dc.date.issued2022-01-17
dc.date.updated2022-02-07T12:31:53Z
dc.description.abstractThe metabolism of dietary tryptophan occurs locally in the gut primarily via host enzymes, with similar to 5% metabolized by gut microbes. Three major tryptophan metabolic pathways are serotonin (beyond the scope of this review), indole, kynurenine and related derivatives. We introduce the gut microbiome, dietary tryptophan and the potential interplay of host and bacterial enzymes in tryptophan metabolism. Examples of bacterial transformation to indole and its derivative indole-3 propionic acid demonstrate associations with human metabolic disease and gut permeability, although causality remains to be determined. This review will focus on less well-known data, suggestive of local generation and functional significance in the gut, where kynurenine is converted to kynurenic acid and xanthurenic acid via enzymatic action present in both host and bacteria. Our functional data demonstrate a limited effect on intestinal epithelial cell monolayer permeability and on healthy mouse ileum. Other data suggest a modulatory effect on the microbiome, potentially in pathophysiology. Supportive of this, we found that the expression of mRNA for three kynurenine pathway enzymes were increased in colon from high-fat-fed mice, suggesting that this host pathway is perturbed in metabolic disease. These data, along with that from bacterial genomic analysis and germ-free mice, confirms expression and functional machinery of enzymes in this pathway. Therefore, the host and microbiota may play a significant dual role in either the production or regulation of these kynurenine metabolites which, in turn, can influence both host and microbiome, especially in the context of obesity and intestinal permeability.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHyland, N. P., Cavanaugh, C. R. and Hornby, P. J. (2022) 'Emerging effects of tryptophan pathway metabolites and intestinal microbiota on metabolism and intestinal function', Amino Acids, 54, pp. 57-70. doi: 10.1007/s00726-022-03123-xen
dc.identifier.doi10.1007/s00726-022-03123-xen
dc.identifier.eissn438-2199
dc.identifier.endpage70en
dc.identifier.issn0939-4451
dc.identifier.journaltitleAmino Acidsen
dc.identifier.startpage57en
dc.identifier.urihttps://hdl.handle.net/10468/12531
dc.identifier.volume54en
dc.language.isoenen
dc.publisherSpringer Wienen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Industry Fellowship/15/IFB/3578/IE/Validation of Intestinal Tryptophan Metabolism as a Therapeutic Target in Obesity and Insulin Resistance/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.rights© 2022, the Authors, under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature. This is a post-peer-review, pre-copyedit version of an article published in Amino Acids. The final authenticated version is available online at: https://doi.org/10.1007/s00726-022-03123-xen
dc.subjectMicrobiomeen
dc.subjectIntestinal permeabilityen
dc.subjectColonen
dc.subjectMetabolic endotoxemiaen
dc.subjectKynurenineen
dc.subjectIndoleen
dc.subjectObesityen
dc.subjectType 2 diabetesen
dc.subjectAryl-hydrocarbon receptoren
dc.subjectHuman gut microbiotaen
dc.subjectKynurenic aciden
dc.subjectGlutamate receptorsen
dc.subjectIndoleamine 2,3-dioxygenaseen
dc.subjectBarrier functionen
dc.subjectProteinen
dc.subjectDieten
dc.subjectExpressionen
dc.subjectSecretionen
dc.titleEmerging effects of tryptophan pathway metabolites and intestinal microbiota on metabolism and intestinal functionen
dc.typeArticle (peer-reviewed)en
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