Dietary Fatty Acids Modulate Gut Microbiota-Derived Trimethylamine-N-Oxide: Potential Mechanisms and Future Perspective.

High-fat diets are known to contribute to metabolic disorders such as obesity, diabetes, and cardiovascular diseases, partly through alterations in gut microbiota composition. However, the impact of dietary fat on gut microbiota depends on fat composition, with both the degree of saturation and chain length of fatty acids playing essential roles in modulating microbial populations. Saturated long-chain fatty acids have been shown to promote the production of trimethylamine (TMA), a precursor of trimethylamine N-oxide (TMAO), an emerging gut microbiota-derived biomarker associated with cardiovascular disease. These effects occur through multiple mechanisms, including increased colonic oxygen levels and taurine-conjugated bile acids, which promote pathways that favor TMA-producing bacteria. In contrast, short-chain fatty acids (SCFAs) and omega-3 polyunsaturated fatty acids exert beneficial effects by altering pH and supporting SCFA-producing bacteria, thereby reducing levels of TMA-producing bacteria. Given the influence of gut microbial communities and their metabolites on the onset of metabolic disorders, dietary strategies that modulate the microbiota and its metabolic products through optimized fatty acid composition represent promising therapeutic approaches for preventing conditions such as cardiovascular disease.