Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan 410078, China.
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
ACS Chem Neurosci. 2022 Apr 6;13(7):1065-1081. doi: 10.1021/acschemneuro.2c00082. Epub 2022 Mar 21.
Gut dysbiosis is observed in Alzheimer's disease (AD) and is frequently associated with AD-induced metabolic dysfunction. However, the extent and specific underlying molecular mechanisms triggered by alterations of gut microbiota composition and function mediating AD-induced metabolic dysfunction in AD remain incompletely uncovered. Here, we indicate that ( is abundant in AD patients with relative metabolic dysfunction. Fecal microbiota transplantation from the AD patients promoted metabolic dysfunction in mice and increased gut permeability. increased gut permeability through activation of the TLR4/Myd88 inflammation pathway in a p53-dependent manner, leading to metabolic dysfunction. Moreover, p53 deficiency reduced bile acid concentration, leading to an increased abundance of colonization. Overall, these data identify as a key promoter of AD-induced metabolic dysfunction.
肠道菌群失调在阿尔茨海默病(AD)中观察到,并且经常与 AD 引起的代谢功能障碍相关。然而,由肠道微生物群落组成和功能改变引发的,介导 AD 引起的代谢功能障碍的程度和特定的潜在分子机制在很大程度上仍未被揭示。在这里,我们表明, 在 AD 患者中相对代谢功能障碍的患者中含量丰富。来自 AD 患者的粪便微生物群移植促进了小鼠的代谢功能障碍,并增加了肠道通透性。 通过 TLR4/Myd88 炎症途径的激活,以依赖 p53 的方式增加肠道通透性,导致代谢功能障碍。此外,p53 缺乏会降低胆汁酸浓度,导致 的定植丰度增加。总的来说,这些数据确定 是 AD 引起的代谢功能障碍的关键促进因子。