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[This article belongs to Volume - 70, Issue - 2]
Published on : 2025-02-14 13:59:52
Article Code: AMJ-14-02-2025-12311
Title : The Gut Microbiome-Derived Metabolite TMAO as a Modulator of Immune Checkpoint Inhibitor Efficacy in Non-Small Cell Lung Cancer
Author(s) : Dr. Jean-Pierre Dubois, Dr. Mei Ling Chen
Abstract :
Gut microbiome composition influences immunotherapy responses, yet specific metabolite mediators remain
unidentified. We show that trimethylamine N-oxide (TMAO), produced by gut microbiota from dietary choline,
directly impairs CD8+ T-cell effector function through mTORC1 pathway inhibition and mitochondrial dysfunction.
Elevated plasma TMAO levels (>6.5 μM) correlated with poor progression-free survival (PFS) in 240 NSCLC patients
receiving pembrolizumab. Conversely, pharmacological blockade of TMAO synthesis using iodomethylcholine (IMC)
or fecal microbiota transplantation from low-TMAO donors restored anti-tumor immunity and enhanced anti-PD-1
efficacy in murine models. Dietary intervention and microbial modulation represent actionable strategies to optimize
immunotherapy outcomes.