Gut microbiota-derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxia
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224008551 |
| _version_ | 1827284850477891584 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yichen Yan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T10:04:17Z |
| format | Article |
| id | doaj.art-817bf388ae944f97976d57fafff46693 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T10:04:17Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-817bf388ae944f97976d57fafff466932024-04-13T04:21:38ZengElsevieriScience2589-00422024-05-01275109633Gut microbiota-derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxiaYichen Yan0Xiaoli Zheng1Gang Liu2Guocheng Shi3Cong Li4Hongtong Chen5Xiaomin He6Kana Lin7Zhaohui Deng8Hao Zhang9Wei-Guang Li10Huiwen Chen11Xiaoping Tong12Zhongqun Zhu13Department of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Center for Brain Science, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaSongjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Center for Brain Science, Shanghai Children’s Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCenter for Brain Science, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Pharmacy, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Gastroenterology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCenter for Brain Science, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authorSongjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Center for Brain Science, Shanghai Children’s Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authorDepartment of Cardiothoracic Surgery, Congenital Heart Center, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Center for Brain Science, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224008551MicrobiomeMolecular biologyNeurosciencePhysiology |
| spellingShingle | 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 Gut microbiota-derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxia iScience Microbiome Molecular biology Neuroscience Physiology |
| title | Gut microbiota-derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxia |
| title_full | Gut microbiota-derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxia |
| title_fullStr | Gut microbiota-derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxia |
| title_full_unstemmed | Gut microbiota-derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxia |
| title_short | Gut microbiota-derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxia |
| title_sort | gut microbiota derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxia |
| topic | Microbiome Molecular biology Neuroscience Physiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224008551 |
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