Zhang Yiying, Shen Yuan, Liufu Ning, Liu Ling, Li Wei, Shi Zhongyong, Zheng Hailin, Mei Xinchun, Chen Chih-Yu, Jiang Zengliang, Abtahi Shabnamsadat, Dong Yuanlin, Liang Feng, Shi Yujiang, Cheng Leo, Yang Guang, Kang Jing X, Wilkinson Jeremy, Xie Zhongcong
Massachusetts General Hospital.
Tenth People's Hospital of Tongji University.
Res Sq. 2023 Apr 28:rs.3.rs-2790988. doi: 10.21203/rs.3.rs-2790988/v1.
Spouses of Alzheimer's disease (AD) patients are at higher risk of developing AD dementia, but the reasons and underlying mechanism are unknown. One potential factor is gut microbiota dysbiosis, which has been associated with AD. However, it remains unclear whether the gut microbiota dysbiosis can be transmitted to non-AD individuals and contribute to the development of AD pathogenesis and cognitive impairment. The present study found that co-housing wild-type mice with AD transgenic mice or giving them AD transgenic mice feces caused AD-associated gut microbiota dysbiosis, Tau phosphorylation, and cognitive impairment. Gavage with Lactobacillus and Bifidobacterium restored these changes. The oral and gut microbiota of AD patient partners resembled that of AD patients but differed from healthy controls, indicating the transmission of oral and gut microbiota and its impact on cognitive function. The underlying mechanism of these findings includes that the butyric acid-mediated acetylation of GSK3β at lysine 15 regulated its phosphorylation at serine 9, consequently impacting Tau phosphorylation. These results provide insight into a potential link between gut microbiota dysbiosis and AD and underscore the need for further research in this area.
阿尔茨海默病（AD）患者的配偶患AD痴呆症的风险更高，但原因和潜在机制尚不清楚。一个潜在因素是肠道微生物群失调，这与AD有关。然而，尚不清楚肠道微生物群失调是否会传染给非AD个体，并导致AD发病机制和认知障碍的发展。本研究发现，将野生型小鼠与AD转基因小鼠共同饲养或给它们喂食AD转基因小鼠的粪便会导致与AD相关的肠道微生物群失调、Tau蛋白磷酸化和认知障碍。用乳酸杆菌和双歧杆菌灌胃可恢复这些变化。AD患者配偶的口腔和肠道微生物群与AD患者相似，但与健康对照不同，这表明口腔和肠道微生物群的传播及其对认知功能的影响。这些发现的潜在机制包括丁酸介导的GSK3β赖氨酸15位的乙酰化调节其丝氨酸9位的磷酸化，从而影响Tau蛋白磷酸化。这些结果为肠道微生物群失调与AD之间的潜在联系提供了见解，并强调了该领域进一步研究的必要性。
