Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 5 March 2021 / Approved: 8 March 2021 / Online: 8 March 2021 (15:55:29 CET)

A peer-reviewed article of this Preprint also exists.

Wyatt, M.; Greathouse, K.L. Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer. Nutrients 2021, 13, 1189. Wyatt, M.; Greathouse, K.L. Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer. Nutrients 2021, 13, 1189.

Journal reference: Nutrients 2021, 13, 1189
DOI: 10.3390/nu13041189

Abstract

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.

Keywords

Tryptophan metabolism; Kynurenine; Indoleamine 2,3-dioxygenase; Aryl hydrocarbon receptor; Microbiome; Indole; Colon cancer.

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