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

Abstract

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.

• Authors: 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
• Journal: iScience (iScience) Vol. 27 Issue 5 Pg. 109633 (May 17 2024) ISSN: 2589-0042 [Electronic] United States
• PMID: 38638560 (Publication Type: Journal Article)
• Copyright: © 2024 The Authors. Published by Elsevier Inc.