Combined fecal microbiota transplantation and adipose-derived stem cells protect the blood-spinal cord barrier after spinal cord injury
- 1Division of Spine, Department of Orthopedics, The Affiliated Guangdong Second Provincial General Hospital of Jinan University
- 2Department of Cardiovascular, Liwan Central Hospital of Guangzhou
- 3Department of Orthopedics, First Affiliated Hospital of Gannan Medical University
Abstract
Background: Blood–spinal cord barrier (BSCB) disruption and neuroinflammation contribute to secondary injury after spinal cord injury (SCI). Fecal microbiota transplantation (FMT) and human adipose-derived stem cells (hADSCs) each show therapeutic potential, but the effects of combined treatment and the influence of fecal soluble components on hADSCs secretory activity remain unclear.
Methods: A T9 forceps-crush SCI model was established in C57BL/6J mice to compare FMT, intralesional hADSCs transplantation, and their combination. Functional recovery, BSCB permeability, neuroinflammation, lesion pathology, and neural tissue preservation were evaluated. Exploratory 16S rRNA sequencing was performed at 35 days post-injury. In vitro , hADSCs were exposed to filtered fecal material from healthy donor mice, and their conditioned medium was applied to oxygen–glucose deprivation/reoxygenation-injured bEnd.3 endothelial cells.
Results: Combined FMT and hADSCs treatment improved locomotor recovery, attenuated BSCB leakage and neuroinflammatory responses, and preserved neural tissue, with several outcomes greater than either monotherapy. Exploratory 16S analysis identified treatment-associated differences in microbial richness and overall community composition. Fecal-filtrate preconditioning increased hADSCs secretion of VEGF, HGF, and IL-10 by 2.3-, 2.2-, and 1.8-fold, respectively. Conditioned medium from preconditioned hADSCs improved wound closure, preserved ZO-1 and Claudin-5 signals, and reduced endothelial monolayer permeability after OGD/R. IL-10 silencing partially attenuated these protective effects.
Conclusions: Combined FMT and hADSCs treatment was associated with greater BSCB preservation, reduced neuroinflammation, and improved functional recovery after SCI. In vitro , soluble components of healthy-donor fecal filtrate modulated hADSCs secretory activity and enhanced endothelial protection. These findings do not establish that oral FMT reprograms transplanted hADSCs in vivo or that microbiota alterations mediate the combined therapeutic effect.
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BibTeX
@article{tang2026combined,
title = {{Combined fecal microbiota transplantation and adipose-derived stem cells protect the blood-spinal cord barrier after spinal cord injury}},
author = {Zhicheng Tang and Junjie Chen and Daming Peng and Biling Mo and Shun Yao and Huan Xie and Daoyuan Jiang and Wentao Zhuo and Hui Zhang and Zhilai Zhou},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1877863},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1877863/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Combined fecal microbiota transplantation and adipose-derived stem cells protect the blood-spinal cord barrier after spinal cord injury
AU - Zhicheng Tang
AU - Junjie Chen
AU - Daming Peng
AU - Biling Mo
AU - Shun Yao
AU - Huan Xie
AU - Daoyuan Jiang
AU - Wentao Zhuo
AU - Hui Zhang
AU - Zhilai Zhou
PY - 2026
DA - 2026/10/13
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1877863
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1877863/full
AB - Background: Blood–spinal cord barrier (BSCB) disruption and neuroinflammation contribute to secondary injury after spinal cord injury (SCI). Fecal microbiota transplantation (FMT) and human adipose-derived stem cells (hADSCs) each show therapeutic potential, but the effects of combined treatment and the influence of fecal soluble components on hADSCs secretory activity remain unclear. Methods: A T9 forceps-crush SCI model was established in C57BL/6J mice to compare FMT, intralesional hADSCs transplantation, and their combination. Functional recovery, BSCB permeability, neuroinflammation, lesion pathology, and neural tissue preservation were evaluated. Exploratory 16S rRNA sequencing was performed at 35 days post-injury. In vitro , hADSCs were exposed to filtered fecal material from healthy donor mice, and their conditioned medium was applied to oxygen–glucose deprivation/reoxygenation-injured bEnd.3 endothelial cells. Results: Combined FMT and hADSCs treatment improved locomotor recovery, attenuated BSCB leakage and neuroinflammatory responses, and preserved neural tissue, with several outcomes greater than either monotherapy. Exploratory 16S analysis identified treatment-associated differences in microbial richness and overall community composition. Fecal-filtrate preconditioning increased hADSCs secretion of VEGF, HGF, and IL-10 by 2.3-, 2.2-, and 1.8-fold, respectively. Conditioned medium from preconditioned hADSCs improved wound closure, preserved ZO-1 and Claudin-5 signals, and reduced endothelial monolayer permeability after OGD/R. IL-10 silencing partially attenuated these protective effects. Conclusions: Combined FMT and hADSCs treatment was associated with greater BSCB preservation, reduced neuroinflammation, and improved functional recovery after SCI. In vitro , soluble components of healthy-donor fecal filtrate modulated hADSCs secretory activity and enhanced endothelial protection. These findings do not establish that oral FMT reprograms transplanted hADSCs in vivo or that microbiota alterations mediate the combined therapeutic effect.
SN - 1664-3224
ER -