Yingli Jing1,2, Fan Bai1,2, Yan Yu3,4, Limiao Wang1,2, Degang Yang1,2, Chao Zhang1,2, Chuan Qin1,2, Mingliang Yang1,2, Dong Zhang5,6,7, Yanbing Zhu5,6,7, Jianjun Li8,9, Zhiguo Chen10,11. 1. China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China. 2. Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China. 3. China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China. yuyancrrc@163.com. 4. Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China. yuyancrrc@163.com. 5. Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China. 6. Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China. 7. Beijing Clinical Research Institute, Beijing, China. 8. China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, and School of Rehabilitation Medicine, Capital Medical University, Beijing, China. crrc100@163.com. 9. Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China. crrc100@163.com. 10. Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China. chenzhiguo@gmail.com. 11. Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, and Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China. chenzhiguo@gmail.com.
Abstract
BACKGROUND: Spinal cord injury (SCI) patients display disruption of gut microbiome, and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) from healthy uninjured mice into SCI mice may exert a neuroprotective effect. RESULTS: FMT facilitated functional recovery, promoted neuronal axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility in SCI mice. High-throughput sequencing revealed that levels of phylum Firmicutes, family Christensenellaceae, and genus Butyricimonas were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT downregulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut following SCI. CONCLUSION: Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs. Video Abstract.
BACKGROUND:Spinal cord injury (SCI) patients display disruption of gut microbiome, and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) from healthy uninjured mice into SCI mice may exert a neuroprotective effect. RESULTS: FMT facilitated functional recovery, promoted neuronal axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility in SCI mice. High-throughput sequencing revealed that levels of phylum Firmicutes, family Christensenellaceae, and genus Butyricimonas were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT downregulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut following SCI. CONCLUSION: Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs. Video Abstract.
Entities:
Keywords:
Fecal microbiota transplantation; GI function; Gut microbiota; Neuroinflammation; Neurological function
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