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Association of gut microbiota with cerebral cortex and cerebrovascular abnormality in human mild traumatic brain injury

Lijun Bai, Tianhui Li, Ming Zhang, Shan Wang, Shuoqiu Gan, Xiaoyan Jia, Xuefei Yang, Yinxiang Sun, Feng Xiong, Bo Yin, Yi Ren, Guanghui Bai, Zhihan Yan, Xin Mu, View ORCID ProfileFeng Zhu
doi: https://doi.org/10.1101/2020.07.19.211227
Lijun Bai
1The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’ an, China
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Tianhui Li
1The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’ an, China
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Ming Zhang
2Department of Medical Imaging, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Shan Wang
1The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’ an, China
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Shuoqiu Gan
1The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’ an, China
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Xiaoyan Jia
1The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’ an, China
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Xuefei Yang
1The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’ an, China
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Yinxiang Sun
2Department of Medical Imaging, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Feng Xiong
1The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’ an, China
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Bo Yin
3Department of Neurosurgery, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China
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Yi Ren
4Department of Rehabilitation Medicine, the Hanzhong Central Hospital, Hanzhong 723000, China
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Guanghui Bai
5Department of Radiology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China
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Zhihan Yan
5Department of Radiology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China
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Xin Mu
6Center for Translational Medicine, the First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an 710061, China
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Feng Zhu
6Center for Translational Medicine, the First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an 710061, China
7Center for Brain Science, the First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an 710061, China
8Clinical Research Center for Psychiatric Medicine of Shaanxi Province, the First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an 710061, China
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  • ORCID record for Feng Zhu
  • For correspondence: zhufeng0714@163.com
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Abstract

Key roles of the gut–brain axis in brain injury development have been suggested in various mouse models; however, little is known about its functional significance in human mild traumatic brain injury (TBI). Here, we decipher this axis by profiling the gut microbiota in 98 acute mild TBI patients and 62 matched controls, and subgroup of them also measured circulating mediators and applied neuroimaging. Mild TBI patients had increased α-diversity and different overall microbial compositions compared with controls. 25-microbial genus classifiers distinguish patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.889, while adding serum mediators and neuroimaging features further improved performance even in a small sample size (AUC = 0.969). Numerous correlations existed between gut bacteria, aberrant cortical thickness and cerebrovascular injury. Co-occurrence network analysis revealed two unique gut–brain axes in patients: 1) altered intestinal Lachnospiraceae_NK4A136_group and Eubacterium_ruminantium_group-increased serum GDNF-subcallosal hypertrophy and cerebrovascular injury; 2) decreased intestinal Eubacterium_xylanophilum_group–upregulated IL-6–thinned anterior insula. Our findings provide a new integrated mechanistic understanding and diagnostic model of mild TBI.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted July 20, 2020.
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Association of gut microbiota with cerebral cortex and cerebrovascular abnormality in human mild traumatic brain injury
Lijun Bai, Tianhui Li, Ming Zhang, Shan Wang, Shuoqiu Gan, Xiaoyan Jia, Xuefei Yang, Yinxiang Sun, Feng Xiong, Bo Yin, Yi Ren, Guanghui Bai, Zhihan Yan, Xin Mu, Feng Zhu
bioRxiv 2020.07.19.211227; doi: https://doi.org/10.1101/2020.07.19.211227
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Association of gut microbiota with cerebral cortex and cerebrovascular abnormality in human mild traumatic brain injury
Lijun Bai, Tianhui Li, Ming Zhang, Shan Wang, Shuoqiu Gan, Xiaoyan Jia, Xuefei Yang, Yinxiang Sun, Feng Xiong, Bo Yin, Yi Ren, Guanghui Bai, Zhihan Yan, Xin Mu, Feng Zhu
bioRxiv 2020.07.19.211227; doi: https://doi.org/10.1101/2020.07.19.211227

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