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Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer

Tryptophan metabolism, via the kynurenine (Kyn) pathway, and microbial transformation of tryptophan to indolic compounds are fundamental for host health; both of which are altered in colon carcinogenesis. Alterations in tryptophan metabolism begin early in colon carcinogenesis as an adaptive mechani...

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Detalles Bibliográficos
Autores principales: Wyatt, Madhur, Greathouse, K. Leigh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066279/
https://www.ncbi.nlm.nih.gov/pubmed/33916690
http://dx.doi.org/10.3390/nu13041189
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author Wyatt, Madhur
Greathouse, K. Leigh
author_facet Wyatt, Madhur
Greathouse, K. Leigh
author_sort Wyatt, Madhur
collection PubMed
description Tryptophan metabolism, via the kynurenine (Kyn) pathway, and microbial transformation of tryptophan to indolic compounds are fundamental for host health; both of which are altered in colon carcinogenesis. Alterations in tryptophan metabolism begin early in colon carcinogenesis as an adaptive mechanism for the tumor to escape immune surveillance and metastasize. The microbial community is a key part of the tumor microenvironment and influences cancer initiation, promotion and treatment response. A growing awareness of the impact of the microbiome on tryptophan (Trp) metabolism in the context of carcinogenesis has prompted this review. We first compare the different metabolic pathways of Trp under normal cellular physiology to colon carcinogenesis, in both the host cells and the microbiome. Second, we review how the microbiome, specifically indoles, influence host tryptophan pathways under normal and oncogenic metabolism. We conclude by proposing several dietary, microbial and drug therapeutic modalities that can be utilized in combination to abrogate tumorigenesis.
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spelling pubmed-80662792021-04-25 Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer Wyatt, Madhur Greathouse, K. Leigh Nutrients Review Tryptophan metabolism, via the kynurenine (Kyn) pathway, and microbial transformation of tryptophan to indolic compounds are fundamental for host health; both of which are altered in colon carcinogenesis. Alterations in tryptophan metabolism begin early in colon carcinogenesis as an adaptive mechanism for the tumor to escape immune surveillance and metastasize. The microbial community is a key part of the tumor microenvironment and influences cancer initiation, promotion and treatment response. A growing awareness of the impact of the microbiome on tryptophan (Trp) metabolism in the context of carcinogenesis has prompted this review. We first compare the different metabolic pathways of Trp under normal cellular physiology to colon carcinogenesis, in both the host cells and the microbiome. Second, we review how the microbiome, specifically indoles, influence host tryptophan pathways under normal and oncogenic metabolism. We conclude by proposing several dietary, microbial and drug therapeutic modalities that can be utilized in combination to abrogate tumorigenesis. MDPI 2021-04-03 /pmc/articles/PMC8066279/ /pubmed/33916690 http://dx.doi.org/10.3390/nu13041189 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Wyatt, Madhur
Greathouse, K. Leigh
Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer
title Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer
title_full Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer
title_fullStr Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer
title_full_unstemmed Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer
title_short Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer
title_sort targeting dietary and microbial tryptophan-indole metabolism as therapeutic approaches to colon cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066279/
https://www.ncbi.nlm.nih.gov/pubmed/33916690
http://dx.doi.org/10.3390/nu13041189
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