Li Xin, Sun Bohan, Qin Yanting, Yue Fangfang, Lü Xin
College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Shaanxi Engineering Research Centre of Dairy Products Quality, Safety and Health, Yangling, Shaanxi, China.
Mol Nutr Food Res. 2025 Feb;69(3):e202400577. doi: 10.1002/mnfr.202400577. Epub 2025 Jan 10.
Fecal microbiota transplantation (FMT) could significantly alter the recipient's gut bacteria composition and attenuate obesity and obesity-related metabolic syndromes. DL-norvaline is a nonproteinogenic amino acid and possesses anti-obesity potential. However, the specific mechanisms by which gut microbiota might mediate beneficial effects of DL-norvaline have not been completely elucidated. In this study, DL-norvaline-mediated FMT upregulated the beneficial bacteria (Clostridia_UCG_014, Christensenellales, Bacilli, Ileibacterium, Dubosiella, Lactobacillus, Muribaculaceae, and Bacteroidaceae) and downregulated the harmful bacteria (Tuzzerella and Marinifilaceae), further intestinal inflammation, oxidative stress, and intestinal barrier were alleviated as well as short chain fatty acids levels were increased, thus alleviating glucose and insulin metabolism, improving biochemical indexes and energy metabolism and decreasing body weight gain and tissue weight. However, heat-inactivated FMT did not demonstrate any of those improvements in obese mice. Notably, both DL-norvaline-mediated FMT and heat-inactivated FMT increased Bacteroidaceae and Muribaculaceae, this being a signature of alterations to the gut microbiota marker caused by DL-norvaline. Therefore, the beneficial effects of DL-norvaline were transmissible via FMT. This study highlighted the pivotal involvement of the gut microbiota in the development of obesity and provided a novel insight into the underlying mechanisms of FMT, thereby potentially enhancing the efficacy and refinement of FMT utilization.
粪便微生物群移植（FMT）可显著改变受体的肠道细菌组成，并减轻肥胖及肥胖相关的代谢综合征。DL-正缬氨酸是一种非蛋白质氨基酸，具有抗肥胖潜力。然而，肠道微生物群介导DL-正缬氨酸有益作用的具体机制尚未完全阐明。在本研究中，DL-正缬氨酸介导的FMT上调了有益菌（梭菌属_UCG_014、克里斯滕森菌目、芽孢杆菌属、回肠杆菌属、杜波西菌属、乳杆菌属、毛螺菌科和拟杆菌科），下调了有害菌（土栖菌属和海丝菌科），进一步减轻了肠道炎症、氧化应激，改善了肠道屏障，同时短链脂肪酸水平升高，从而缓解了葡萄糖和胰岛素代谢，改善了生化指标和能量代谢，减少了体重增加和组织重量。然而，热灭活的FMT在肥胖小鼠中并未显示出任何这些改善。值得注意的是，DL-正缬氨酸介导的FMT和热灭活的FMT均增加了拟杆菌科和毛螺菌科，这是DL-正缬氨酸引起的肠道微生物群标志物改变的一个特征。因此，DL-正缬氨酸的有益作用可通过FMT传递。本研究强调了肠道微生物群在肥胖发生发展中的关键作用，并为FMT的潜在机制提供了新的见解，从而可能提高FMT的疗效和优化其应用。
