| Trimethylamine-N-oxide (TMAO) is a gut microbiota–derived metabolite produced from dietary precursors such as choline, phosphatidylcholine, and carnitine. In cancer, the current literature points to TMAO as generally pro-tumorigenic in several solid-tumor settings, especially colorectal cancer, hepatocellular carcinoma, and possibly prostate cancer, where it has been linked to higher proliferation, migration, angiogenesis, EMT, and inflammatory signaling. Mechanistically, reported pathways include VEGFA-driven angiogenesis, PI3K/AKT, MAPK, oxidative/inflammatory stress, and metabolic reprogramming. However, the picture is not uniformly one-directional: in some immune-competent models, particularly triple-negative breast cancer and pancreatic cancer, TMAO has been reported to enhance antitumor immunity and improve response to checkpoint blockade. So the fairest summary is that TMAO is usually associated with cancer-promoting biology in tumor-cell–centric studies, but can be context-dependent when the immune microenvironment is considered
-high concentrations of polyphenols (e.g., resveratrol, catechins, quercetin, and quercetin-3-O-glucoside), which act synergistically to protect various target organs from elevated TMAO levels
-clinical studies demonstrated that high-dose atorvastatin (80 mg) or the combination of atorvastatin/ezetimibe or rosuvastatin can significantly reduce TMAO levels, likely due to their direct action on the TMAO-producing gut flora
|