Heinrich-Sanchez Ylenia, Vital Marius
Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany.
Ann Med. 2025 Dec;57(1):2525403. doi: 10.1080/07853890.2025.2525403. Epub 2025 Jul 1.
This study reviews the different steps involved in trimethylamine--oxide (TMAO) formation, a gut microbiota (GM)-derived compound that promotes cardiovascular and chronic kidney disease. The formation of TMAO is a metaorganismal process, where trimethylamine (TMA), produced from the dietary precursors betaine, L-carnitine and choline by various members of GM, is absorbed and subsequently oxidized by hepatic flavin-containing monooxygenases before entering the circulation.
We provide an updated database on members of GM exhibiting different biochemical pathways and give comprehensive insights into tested as well as hypothetical treatment options to reduce TMAO concentrations in the body. Different angles involving nutrition, TMA-producing bacteria, and their enzymes, as well as host enzymes, are discussed.
The study underlines the importance to design personalized therapies taking individual features, such as dietary habits and GM composition, into account. Given the multistep nature of TMAO formation, individualized precision multi-target strategies, for instance, reducing dietary precursors in combination with specific modulations of GM limiting growth/activity of TMA-producing bacteria, might be most successful.
本研究回顾了氧化三甲胺(TMAO)形成过程中的不同步骤,TMAO是一种由肠道微生物群(GM)产生的化合物,可促进心血管疾病和慢性肾脏病。TMAO的形成是一个元生物体过程,其中由GM的各种成员从膳食前体甜菜碱、左旋肉碱和胆碱产生的三甲胺(TMA)被吸收,随后在进入循环之前被肝脏含黄素单加氧酶氧化。
我们提供了一个关于GM成员的最新数据库,这些成员表现出不同的生化途径,并对降低体内TMAO浓度的已测试和假设的治疗方案提供了全面的见解。讨论了涉及营养、产生TMA的细菌及其酶以及宿主酶的不同角度。
该研究强调了设计个性化疗法时考虑个体特征(如饮食习惯和GM组成)的重要性。鉴于TMAO形成的多步骤性质,个性化精准多靶点策略,例如减少膳食前体并结合对GM的特定调节以限制产生TMA的细菌生长/活性,可能最为成功。