Amino acid metabolic reprogramming by gut microbiota: a novel metabolic checkpoint in the tumor microenvironment

Abstract

Abstract The gut microbiota plays a crucial role in human health, significantly influencing various physiological functions such as amino acid metabolism, which is essential for maintaining homeostasis and preventing disease. Recent progress in gut microbiota research has highlighted the intricate relationships between gut microbial communities and host amino acid metabolism, particularly in the context of cancer. This review focuses on consolidating the latest advances regarding how gut microbiota–mediated amino acid metabolism contributes to cancer development and progression. While dysbiosis has been implicated in various diseases, such as metabolic disorders, autoimmune conditions, and neurodegenerative diseases, this review specifically examines the evidence linking gut microbiota and amino acid metabolism to cancer. Current studies suggest that alterations in gut microbial composition can lead to imbalances in amino acid availability and metabolism, thereby influencing systemic inflammation, oxidative stress, and immune responses that may promote tumorigenesis. Despite these insights, significant challenges remain, including identifying specific microbial strains, deciphering their metabolic pathways, and understanding their complex interactions with host factors in cancer progression. This review aims to summarize recent preclinical and clinical investigations elucidating the mechanisms linking the gut microbiota, amino acid metabolism, and cancer, and to evaluate potential therapeutic strategies targeting the gut microbiome to modulate amino acid metabolism and improve cancer treatment outcomes. By highlighting the gut microbiota as a promising target for innovative oncological therapies, this review provides insights into microbiome-based interventions targeting amino acid-related pathways in cancer.