Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice.
Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice.
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亚精胺可改善饮食诱导的肥胖小鼠的肠道屏障完整性和肠道微生物群功能。
DOI：
10.1080/19490976.2020.1832857
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发表时间：
2020-11-09
期刊：
影响因子：
12.2
通讯作者：
Fu Z
中科院分区：
文献类型：
--
作者：
Ma L;Ni Y;Wang Z;Tu W;Ni L;Zhuge F;Zheng A;Hu L;Zhao Y;Zheng L;Fu Z
肥胖与肠道屏障功能受损和肠道菌群失调有关。亚精胺是一种多胺，可作为自噬诱导剂，对衰老相关疾病和代谢功能障碍患者有重要益处。然而，亚精胺对肥胖的作用机制尚不清楚。在这里，我们表明亚精胺摄入量与人类和小鼠的肥胖呈负相关。补充亚精胺可显著减轻饮食性肥胖（DIO）小鼠的体重并改善胰岛素抵抗。这些作用与代谢内毒素血症的减轻和肠道屏障功能的增强有关，可能通过自噬途径和tlr4介导的微生物信号转导介导。此外，亚精胺引起微生物群组成和功能的显著改变。微生物群的消耗损害了功能，而亚精胺改变的微生物群移植可以防止肥胖。这些变化可能部分是由一种产生scfa的细菌Lachnospiraceae NK4A136组驱动的，这种细菌在肥胖受试者中减少，随后在亚精胺的作用下增加。值得注意的是，毛螺科NK4A136组的变化与亚精胺诱导的肠道屏障功能增强显著相关。我们的结果表明，补充亚精胺可能是一种可行的治疗肥胖的方法。
Obesity is associated with impaired intestinal barrier function and dysbiosis of the gut microbiota. Spermidine, a polyamine that acts as an autophagy inducer, has important benefits in patients with aging-associated diseases and metabolic dysfunction. However, the mechanism of spermidine on obesity remains unclear. Here, we show that spermidine intake is negatively correlated with obesity in both humans and mice. Spermidine supplementation causes a significant loss of weight and improves insulin resistance in diet-induced obese (DIO) mice. These effects are associated with the alleviation of metabolic endotoxemia and enhancement of intestinal barrier function, which might be mediated through autophagy pathway and TLR4-mediated microbial signaling transduction. Moreover, spermidine causes the significant alteration of microbiota composition and function. Microbiota depletion compromises function, while transplantation of spermidine-altered microbiota confers protection against obesity. These changes might partly be driven by an SCFA-producing bacterium, Lachnospiraceae NK4A136 group, which was decreased in obese subjects and subsequently increased by spermidine. Notably, the change of Lachnospiraceae NK4A136 group is significantly correlated with enhanced gut barrier function induced by spermidine. Our results indicate that spermidine supplementation may serve as a viable therapy for obesity.
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