Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site
ABSTRACT The primary traumatic event that causes spinal cord injury (SCI) is followed by a progressive secondary injury featured by vascular disruption and ischemia, inflammatory responses and the release of cytotoxic debris, which collectively add to the hostile microenvironment of the lesioned cor...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-06-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00177-22 |
| _version_ | 1818218446553350144 |
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| author | Yingli Jing Fan Bai Limiao Wang Degang Yang Yitong Yan Qiuying Wang Yanbing Zhu Yan Yu Zhiguo Chen |
| author_facet | Yingli Jing Fan Bai Limiao Wang Degang Yang Yitong Yan Qiuying Wang Yanbing Zhu Yan Yu Zhiguo Chen |
| author_sort | Yingli Jing |
| collection | DOAJ |
| description | ABSTRACT The primary traumatic event that causes spinal cord injury (SCI) is followed by a progressive secondary injury featured by vascular disruption and ischemia, inflammatory responses and the release of cytotoxic debris, which collectively add to the hostile microenvironment of the lesioned cord and inhibit tissue regeneration and functional recovery. In a previous study, we reported that fecal microbiota transplantation (FMT) promotes functional recovery in a contusion SCI mouse model; yet whether and how FMT treatment may impact the microenvironment at the injury site are not well known. In the current study, we examined individual niche components and investigated the effects of FMT on microcirculation, inflammation and trophic factor secretion in the spinal cord of SCI mice. FMT treatment significantly improved spinal cord tissue sparing, vascular perfusion and pericyte coverage and blood-spinal cord-barrier (BSCB) integrity, suppressed the activation of microglia and astrocytes, and enhanced the secretion of neurotrophic factors. Suppression of inflammation and upregulation of trophic factors, jointly, may rebalance the niche homeostasis at the injury site and render it favorable for reparative and regenerative processes, eventually leading to functional recovery. Furthermore, microbiota metabolic profiling revealed that amino acids including β-alanine constituted a major part of the differentially detected metabolites between the groups. Supplementation of β-alanine in SCI mice reduced BSCB permeability and increased the number of surviving neurons, suggesting that β-alanine may be one of the mediators of FMT that participates in the modulation and rebalancing of the microenvironment at the injured spinal cord. IMPORTANCE FMT treatment shows a profound impact on the microenvironment that involves microcirculation, blood-spinal cord-barrier, activation of immune cells, and secretion of neurotrophic factors. Analysis of metabolic profiles reveals around 22 differentially detected metabolites between the groups, and β-alanine was further chosen for functional validation experiments. Supplementation of SCI mice with β-alanine significantly improves neuronal survival, and the integrity of blood-spinal cord-barrier at the lesion site, suggesting that β-alanine might be one of the mediators following FMT that has contributed to the recovery. |
| first_indexed | 2024-12-12T07:23:54Z |
| format | Article |
| id | doaj.art-975a91c379ad48918e1747c140c023cb |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-12-12T07:23:54Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-975a91c379ad48918e1747c140c023cb2022-12-22T00:33:12ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-06-0110310.1128/spectrum.00177-22Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion SiteYingli Jing0Fan Bai1Limiao Wang2Degang Yang3Yitong Yan4Qiuying Wang5Yanbing Zhu6Yan Yu7Zhiguo Chen8China Rehabilitation Science Institute, Feng tai District, Beijing, People's Republic of ChinaChina Rehabilitation Science Institute, Feng tai District, Beijing, People's Republic of ChinaChina Rehabilitation Science Institute, Feng tai District, Beijing, People's Republic of ChinaChina Rehabilitation Research Center, Feng tai District, Beijing, People's Republic of ChinaChina Rehabilitation Science Institute, Feng tai District, Beijing, People's Republic of ChinaChina Rehabilitation Science Institute, Feng tai District, Beijing, People's Republic of ChinaExperimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Xicheng District, Beijing, People's Republic of ChinaChina Rehabilitation Science Institute, Feng tai District, Beijing, People's Republic of ChinaCenter of Neural Injury and Repair, Beijing Institute for Brain Disorders, Feng tai District, Beijing, People's Republic of ChinaABSTRACT The primary traumatic event that causes spinal cord injury (SCI) is followed by a progressive secondary injury featured by vascular disruption and ischemia, inflammatory responses and the release of cytotoxic debris, which collectively add to the hostile microenvironment of the lesioned cord and inhibit tissue regeneration and functional recovery. In a previous study, we reported that fecal microbiota transplantation (FMT) promotes functional recovery in a contusion SCI mouse model; yet whether and how FMT treatment may impact the microenvironment at the injury site are not well known. In the current study, we examined individual niche components and investigated the effects of FMT on microcirculation, inflammation and trophic factor secretion in the spinal cord of SCI mice. FMT treatment significantly improved spinal cord tissue sparing, vascular perfusion and pericyte coverage and blood-spinal cord-barrier (BSCB) integrity, suppressed the activation of microglia and astrocytes, and enhanced the secretion of neurotrophic factors. Suppression of inflammation and upregulation of trophic factors, jointly, may rebalance the niche homeostasis at the injury site and render it favorable for reparative and regenerative processes, eventually leading to functional recovery. Furthermore, microbiota metabolic profiling revealed that amino acids including β-alanine constituted a major part of the differentially detected metabolites between the groups. Supplementation of β-alanine in SCI mice reduced BSCB permeability and increased the number of surviving neurons, suggesting that β-alanine may be one of the mediators of FMT that participates in the modulation and rebalancing of the microenvironment at the injured spinal cord. IMPORTANCE FMT treatment shows a profound impact on the microenvironment that involves microcirculation, blood-spinal cord-barrier, activation of immune cells, and secretion of neurotrophic factors. Analysis of metabolic profiles reveals around 22 differentially detected metabolites between the groups, and β-alanine was further chosen for functional validation experiments. Supplementation of SCI mice with β-alanine significantly improves neuronal survival, and the integrity of blood-spinal cord-barrier at the lesion site, suggesting that β-alanine might be one of the mediators following FMT that has contributed to the recovery.https://journals.asm.org/doi/10.1128/spectrum.00177-22fecal microbiota transplantationmicroenvironmentspinal cord injuryvascular repairinflammationβ-alanine |
| spellingShingle | Yingli Jing Fan Bai Limiao Wang Degang Yang Yitong Yan Qiuying Wang Yanbing Zhu Yan Yu Zhiguo Chen Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site Microbiology Spectrum fecal microbiota transplantation microenvironment spinal cord injury vascular repair inflammation β-alanine |
| title | Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site |
| title_full | Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site |
| title_fullStr | Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site |
| title_full_unstemmed | Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site |
| title_short | Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site |
| title_sort | fecal microbiota transplantation exerts neuroprotective effects in a mouse spinal cord injury model by modulating the microenvironment at the lesion site |
| topic | fecal microbiota transplantation microenvironment spinal cord injury vascular repair inflammation β-alanine |
| url | https://journals.asm.org/doi/10.1128/spectrum.00177-22 |
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