Gut microbiota-regulated tryptophan metabolism in breast cancer: mechanisms and therapeutic perspectives

TL;DR

This paper explores how gut bacteria influence breast cancer through tryptophan metabolism and its effects on tumor growth and immune response.

Contribution

It provides a comprehensive review of the gut microbiota-tryptophan metabolism-breast cancer axis and its therapeutic potential.

Findings

Gut microbiota metabolizes tryptophan into bioactive compounds via the kynurenine and indole pathways.

These metabolites influence breast cancer progression through AhR signaling and serotonin receptors.

Modulating this metabolic axis could offer new therapeutic strategies for breast cancer.

Abstract

Breast cancer remains the most commonly diagnosed cancer among women worldwide, and multiple studies now link its development and progression to disturbances in metabolic and immune regulation. Among these factors, the gut microbiota is increasingly recognized as a modulator of host physiology through its metabolism of dietary tryptophan (Trp). Here we focus on the current understanding of the microbial metabolism of Trp, which primarily generates bioactive metabolites through the kynurenine (Kyn) pathway and the indole pathway. These metabolites can serve as endogenous ligands, activating the aryl hydrocarbon receptor (AhR) signaling pathway. They can also promote tumor stem cell characteristics, epithelial-mesenchymal transition (EMT), and metastasis via serotonin receptors (such as HTR1B/1D, HTR2B). The activation of such pathways contributes to the remodeling of the tumor immune microenvironment, alters the functions of immune cells, and directly influences the proliferation, invasion, and metastatic behavior of breast cancer cells. By integrating findings from preclinical and clinical studies, this review organizes current evidence around the “gut microbiota-Trp metabolism-breast cancer” axis and discusses clinical implications and current limitations. Targeting this metabolic network may provide new opportunities for breast cancer prevention and therapeutic intervention.

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