Trimethylamine-<i>N</i>-oxide formation, the bacterial taxa involved and intervention strategies to reduce its concentration in the human body

This study reviews the different steps involved in trimethylamine-<i>N</i>-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.

本研究综述了氧化三甲胺（trimethylamine-N-oxide, TMAO）形成的不同环节——该物质是肠道菌群（gut microbiota, GM）衍生的化合物，可诱发心血管疾病与慢性肾脏病。氧化三甲胺的生成属于超级生物体过程：膳食前体物甜菜碱、左旋肉碱与胆碱经肠道菌群不同菌种代谢产生三甲胺（trimethylamine, TMA），后者被宿主吸收后，会在肝脏黄素单加氧酶的作用下发生氧化，随后进入血液循环。本研究提供了一份经过更新的数据库，收录了具备不同生化通路的肠道菌群菌种，并全面梳理了经实验验证及假说性的体内TMAO浓度降低治疗方案。研究探讨了涵盖营养调控、产三甲胺细菌及其酶类，以及宿主酶类在内的多个研究视角。本研究强调，设计个性化治疗方案时需兼顾个体特征，例如饮食习惯与肠道菌群组成，这一点至关重要。鉴于氧化三甲胺的生成过程具有多步骤特性，个体化精准多靶点策略或可取得最佳疗效——例如在减少膳食前体物摄入的同时，对肠道菌群进行特异性调控，以抑制产三甲胺细菌的生长与活性。

搜集汇总

背景与挑战

背景概述

该数据集综述了肠道微生物代谢物TMAO的形成机制，涉及细菌分类和干预策略，旨在降低人体内TMAO浓度以预防心血管和慢性肾病。它提供了更新后的微生物生化途径数据库，并讨论了个体化多目标治疗策略，包括饮食调整和微生物调控。