Gut microbiota-derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxia

Autor: Yichen Yan, Xiaoli Zheng, Gang Liu, Guocheng Shi, Cong Li, Hongtong Chen, Xiaomin He, Kana Lin, Zhaohui Deng, Hao Zhang, Wei-Guang Li, Huiwen Chen, Xiaoping Tong, Zhongqun Zhu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 5, Pp 109633- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.109633
Popis: Summary: Chronic hypoxia, common in neonates, disrupts gut microbiota balance, which is crucial for brain development. This study utilized cyanotic congenital heart disease (CCHD) patients and a neonatal hypoxic rat model to explore the association. Both hypoxic rats and CCHD infants exhibited brain immaturity, white matter injury (WMI), brain inflammation, and motor/learning deficits. Through 16s rRNA sequencing and metabolomic analysis, a reduction in B. thetaiotaomicron and P. distasonis was identified, leading to cholic acid accumulation. This accumulation triggered M1 microglial activation and inflammation-induced WMI. Administration of these bacteria rescued cholic acid-induced WMI in hypoxic rats. These findings suggest that gut microbiota-derived cholic acid mediates neonatal WMI and brain inflammation, contributing to brain immaturity under chronic hypoxia. Therapeutic targeting of these bacteria provides a non-invasive intervention for chronic hypoxia patients.
Databáze: Directory of Open Access Journals