Lu Manman, Yang Yuhui, Xu Yuncong, Wang Xiaoyue, Li Bo, Le Guowei, Xie Yanli
National Engineering Laboratory/Key Laboratory of Henan Province, College of Food Science and Engineering, Henan University of Technology, Zhengzhou 450001, China.
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
Nutrients. 2023 Jan 1;15(1):206. doi: 10.3390/nu15010206.
Dietary methionine restriction (MR) has been shown to decrease plasma trimethylamine-N-oxide (TMAO) levels in high-fat diet mice; however, the specific mechanism used is unknown. We speculated that the underlying mechanism is related with the gut microbiota, and this study aimed to confirm the hypothesis. In this study, we initially carried out an in vitro fermentation experiment and found that MR could reduce the ability of gut microbiota found in the contents of healthy mice and the feces of healthy humans to produce trimethylamine (TMA). Subsequently, mice were fed a normal diet (CON, 0.20% choline + 0.86% methionine), high-choline diet (H-CHO, 1.20% choline + 0.86% methionine), or high-choline + methionine-restricted diet (H-CHO+MR, 1.20% choline + 0.17% methionine) for 3 months. Our results revealed that MR decreased plasma TMA and TMAO levels in H-CHO-diet-fed mice without changing hepatic FMO3 gene expression and enzyme activity, significantly decreased TMA levels and expression of choline TMA-lyase () and its activator , and decreased CutC activity in the intestine. Moreover, MR significantly decreased the abundance of TMA-producing bacteria, including ( phylum) and ( phylum), and significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria and SCFA levels. Furthermore, both MR and sodium butyrate supplementation significantly inhibited bacterial growth, down-regulated gene expression levels in TMA-producing bacteria, including and and decreased TMA production from bacterial growth under in vitro anaerobic fermentation conditions. In conclusion, dietary MR alleviates choline-induced TMAO elevation by manipulating gut microbiota in mice and may be a promising approach to reducing circulating TMAO levels and TMAO-induced atherosclerosis.
饮食蛋氨酸限制（MR）已被证明可降低高脂饮食小鼠的血浆三甲胺 - N - 氧化物（TMAO）水平；然而，所采用的具体机制尚不清楚。我们推测其潜在机制与肠道微生物群有关，本研究旨在证实这一假设。在本研究中，我们首先进行了体外发酵实验，发现MR可降低健康小鼠内容物和健康人类粪便中肠道微生物群产生三甲胺（TMA）的能力。随后，将小鼠分别喂食正常饮食（CON，0.20%胆碱 + 0.86%蛋氨酸）、高胆碱饮食（H - CHO，1.20%胆碱 + 0.86%蛋氨酸）或高胆碱 + 蛋氨酸限制饮食（H - CHO+MR，1.20%胆碱 + 0.17%蛋氨酸）3个月。我们的结果显示，MR降低了喂食H - CHO饮食小鼠的血浆TMA和TMAO水平，而未改变肝脏FMO3基因表达和酶活性，显著降低了TMA水平以及胆碱TMA裂解酶（）及其激活剂的表达，并降低了肠道中的CutC活性。此外，MR显著降低了产生TMA的细菌丰度，包括（门）和（门），并显著增加了产生短链脂肪酸（SCFA）的细菌丰度和SCFA水平。此外，MR和丁酸钠补充均显著抑制细菌生长，下调了包括和在内的产生TMA细菌中的基因表达水平，并在体外厌氧发酵条件下降低了细菌生长产生的TMA。总之，饮食MR通过操纵小鼠肠道微生物群减轻胆碱诱导的TMAO升高，可能是降低循环TMAO水平和TMAO诱导的动脉粥样硬化的一种有前景的方法。
