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Ketogenic Diet Alleviates Colorectal Cancer by Attenuating Macrophage M2 Polarisation Triggered by Oncometabolite MMA
Yang Lu1,2, Bo Shi1, Jinmiao Chen1
1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Abstract:
Proposed mechanism of the ketogenic diet-microbiota-MMA-immune axis in CRC. (Part 1) A ketogenic diet remodels gut microbiota homeostasis by depleting MMA-producing bacteria, thereby reducing the accumulation of the oncometabolite (MMA). (Part 2) At the molecular level, MMA acts as a ligand that binds to Rap1, activating the downstream MAPK/ERK signalling cascade. This signalling event drives the transcriptional reprogramming of TAMs towards the pro-tumorigenic M2 phenotype. (Part 3) Clinically, elevated serum MMA in CRC patients correlates with increased M2 macrophage infiltration in the tumour microenvironment and poor prognosis.
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