The intestinal microbial metabolite desaminotyrosine is an anti-inflammatory molecule that modulates local and systemic immune homeostasis
The intestinal microbial metabolite desaminotyrosine is an anti-inflammatory molecule that modulates local and systemic immune homeostasis
复制标题
肠道微生物代谢产物脱氨酪氨酸是一种抗炎分子，可调节局部和全身免疫稳态
DOI：
10.1096/fj.201902900rr
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Wang Yugang
中科院分区：
文献类型：
--
作者：
Wei Yanxia;Gao Jing;Kou Yanbo;Liu Mengnan;Meng Liyuan;Zheng Xingping;Xu Shihong;Liang Ming;Sun Hongxiang;Liu Zhuanzhuan;Wang Yugang
认为肠屏障功能障碍和全身性内毒素血症是肥胖及其相关并发症的驱动因素。然而，什么原因导致屏障功能障碍仍有待阐明。在这里，我们发现高脂饮食（HFD）喂养的小鼠的肠道微生物群降解膳食类黄酮的能力受损，相应地，微生物衍生的类黄酮代谢物脱氨基酪氨酸（DAT）减少。在饮用水中补充DAT能够对抗HFD诱导的体脂量积累和体重增加。这与DAT在维持粘膜免疫稳态以保护屏障完整性中的作用相关。DAT可以以I型干扰素信号依赖性方式减轻葡聚糖硫酸钠（DSS）诱导的粘膜炎症。此外，腹膜内注射DAT保护小鼠免受细菌内毒素诱导的脓毒性休克。总之，我们确定DAT是一种肠道微生物群衍生的抗炎代谢物，其功能是调节局部和全身免疫稳态。我们的数据支持的概念，生态失调是粘膜屏障功能障碍和全身代谢并发症的重要驱动力。
It is considered that intestinal barrier dysfunction and systemic endotoxemia drive obesity and its related complications. However, what causes barrier dysfunction remains to be elucidated. Here, we showed that the gut microbiota from high‐fat diet (HFD)‐fed mice had impaired ability to degrade dietary flavonoids, and in correspondence, the microbial‐derived flavonoid metabolite desaminotyrosine (DAT) was reduced. Supplementation of DAT in the drinking water was able to counter the HFD‐induced body fat mass accumulation and body weight increment. This is correlated with the role of DAT in maintaining mucosal immune homeostasis to protect barrier integrity. DAT could attenuate dextran sodium sulfate (DSS)‐induced mucosal inflammation in a type I interferon signal‐dependent manner. Furthermore, intraperitoneal injection of DAT‐protected mice from bacterial endotoxin‐induced septic shock. Together, we identified DAT as a gut microbiota‐derived anti‐inflammatory metabolite that functions to modulate local and systemic immune homeostasis. Our data support the notion of dysbiosis being an important driving force of mucosal barrier dysfunction and systemic metabolic complications.