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Fecal Microbiota Transplantation-Mediated Ghrelin Restoration Improves Neurological Functions After Traumatic Brain Injury: Evidence from 16S rRNA Sequencing and In Vivo Studies

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Abstract

This study aimed to investigate how gut microbiota dysbiosis impacts the repair of the blood-brain barrier and neurological deficits following traumatic brain injury (TBI). Through 16S rRNA sequencing analysis, we compared the gut microbiota of TBI rats and normal controls, discovering significant differences in abundance, species composition, and ecological function, potentially linked to Ghrelin-mediated brain-gut axis functionality. Further, in vivo experiments showed that fecal microbiota transplantation or Ghrelin injection could block the intracerebral TNF signaling pathway, enhance GLP-1 expression, significantly reduce brain edema post-TBI, promote the repair of the blood-brain barrier, and improve neurological deficits. However, the TNF signaling pathway activation could reverse these beneficial effects. In summary, our research suggests that by restoring the balance of gut microbiota, the levels of Ghrelin can be elevated, leading to the blockade of intracerebral TNF signaling pathway and enhanced GLP-1 expression, thereby mitigating post-TBI blood-brain barrier disruption and neurological injuries.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.

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Funding

This study was funded by the Innovation Foundation of The Affiliated Hospital of Chengdu University (No. CDFYCX202209) and the Research Project of Sichuan Medical Association (No. S21055).

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Author notes

  1. Yamei Zhang and Junying Liu contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Clinical Genetics, Affiliated Hospital of Chengdu University, No. 82, North Section 2, 2nd Ring Road, Chengdu, 610081, People’s Republic of China

    Yamei Zhang, Junying Liu & Zheng Shi

  2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China

    Xinyu Liu

  3. Department of Radiation Protection Medicine, Faculty of Preventive Medicine, Air Force Medical University, Xi’an, 710032, People’s Republic of China

    Yan Zhou

  4. Department of Neurology, Affiliated Hospital of Chengdu University, Chengdu, 610082, People’s Republic of China

    Jia Geng

  5. Institute of Blood Transfusion, Chinese Academy of Medical Sciences, No. 76, Huacai Road, Chenghua District, Chengdu, 610052, Sichuan Province, People’s Republic of China

    Li Ma

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  1. Yamei Zhang
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Contributions

YMZ and JYL planned the experiments; XYL and YZ performed the experiments, prepared the figures, and analyzed the data; YMZ and JYL performed some of the experiments; JG was responsible for the collection of the samples; ZS and LM contributed to drafting the manuscript All authors have read and approved the final submitted manuscript.

Corresponding authors

Correspondence to Yamei Zhang or Li Ma.

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The experimental program and animal use protocol has been approved by the Institutional Animal Care and Use Committee (IACUC) of Chengdu University affiliated Hospital (No. PJ2022-126-01).

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Supplementary Information

ESM 1

Supplemental Fig. 1 The detailed procedures of the in vivo animal experiment. (EPS 2807 kb)

ESM 2

Supplemental Fig. 2 Ecological function prediction of intestinal flora in TBI rats (n = 10) and sham-operated rats (n = 10). A, Functional enrichment of aerobic_chemoheterotrophy in the TBI rats and sham-operated rats. B, Functional enrichment of cellulolysis in the TBI rats and sham-operated rats. C, Functional enrichment of human_pathogens_all in the TBI rats and sham-operated rats. D, Functional enrichment of nitrate-reduction in the TBI rats and sham-operated rats. E, Functional enrichment of xylanolysis in the TBI rats and sham-operated rats. (EPS 1729 kb)

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Zhang, Y., Liu, J., Liu, X. et al. Fecal Microbiota Transplantation-Mediated Ghrelin Restoration Improves Neurological Functions After Traumatic Brain Injury: Evidence from 16S rRNA Sequencing and In Vivo Studies. Mol Neurobiol 61, 919–934 (2024). https://doi.org/10.1007/s12035-023-03595-2

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