Y. Lu, B. Shi, J. Chen, H. Yao, X. Mi, M. Shao, Y. Zhao, L. Meng, Q. Tai, J. Chen, X. Shi, D. Zhou, Y. Yao, et al. (2026). Ketogenic Diet Alleviates Colorectal Cancer by Attenuating Macrophage M2 Polarisation Triggered by Oncometabolite MMA Derived From the Gut Microbiota. Cell proliferation, e70247. https://doi.org/10.1111/cpr.70247

PubMed 42311078

[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.