Spinal cord injury-induced gut dysbiosis influences neurological recovery partly through short-chain fatty acids

作者：Yingli Jing, Degang Yang, Fan Bai, Qiuying Wang, Chao Zhang, Yitong Yan, Zihan Li, Yan Li, Zhiguo Chen, Jianjun Li, Yan Yu · 发表于：npj Biofilms and Microbiomes · 年份：2023 · DOI：10.1038/s41522-023-00466-5 · 被引用次数：65 · 研究领域：Gut microbiota and health、Cerebral Palsy and Movement Disorders、Music Therapy and Health

Spinal cord injury (SCI) can reshape gut microbial composition, significantly affecting clinical outcomes in SCI patients. However, mechanisms regarding gut-brain interactions and their clinical implications have not been elucidated. We hypothesized that short-chain fatty acids (SCFAs), intestinal microbial bioactive metabolites, may significantly affect the gut-brain axis and enhance functional recovery in a mouse model of SCI. We enrolled 59 SCI patients and 27 healthy control subjects and collected samples. Thereafter, gut microbiota and SCFAs were analyzed using 16 S rDNA sequencing and gas chromatography-mass spectrometry, respectively. We observed an increase in Actinobacteriota abundance and a decrease in Firmicutes abundance. Particularly, the SCFA-producing genera, such as Faecalibacterium, Megamonas, and Agathobacter were significantly downregulated among SCI patients compared to healthy controls. Moreover, SCI induced downregulation of acetic acid (AA), propionic acid (PA), and butyric acid (BA) in the SCI group. Fecal SCFA contents were altered in SCI patients with different injury course and injury segments. Main SCFAs (AA, BA, and PA) were administered in combination to treat SCI mice. SCFA supplementation significantly improved locomotor recovery in SCI mice, enhanced neuronal survival, promoted axonal formation, reduced astrogliosis, and suppressed microglial activation. Furthermore, SCFA supplementation downregulated NF-κB signaling while upregulating neurotr...