Metagenomic and metabolomic analysis of gut microbiome's role in spinal cord injury recovery in rats

Jieqi Zhang; Xihan Ying; Rong Hu; Yi Huang; Ruoqi Wang; Lei Wu; Dexiong Han; Ruijie Ma; Kelin He

doi:10.17305/bb.2025.12164

Authors

Jieqi Zhang Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, China https://orcid.org/0009-0001-3392-3421
Xihan Ying Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, China https://orcid.org/0009-0009-8363-4394
Rong Hu Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, China
Yi Huang Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, China https://orcid.org/0009-0007-6359-9435
Ruoqi Wang Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, China https://orcid.org/0009-0006-2491-5039
Lei Wu Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, China; Department of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China https://orcid.org/0000-0001-7055-7865
Dexiong Han Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, China; Department of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China https://orcid.org/0000-0002-9165-1612
Ruijie Ma Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, China; Department of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China https://orcid.org/0000-0002-3480-7772
Kelin He Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, China; Department of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China https://orcid.org/0000-0001-5563-6071

DOI:

https://doi.org/10.17305/bb.2025.12164

Keywords:

Spinal cord injury, SCI, metagenomics, metabolomics, gut microbiome

Abstract

Spinal cord injury (SCI) induces profound systemic changes, including disruptions in gut microbiome composition and host metabolism. This study aimed to investigate the impact of SCI on gut microbial diversity and serum metabolites in rats, and to explore potential microbiome–metabolite interactions that may influence recovery. Male Sprague–Dawley (SD) rats were assigned to either SCI or sham-operated groups. Fecal samples were collected for whole-genome metagenomic sequencing, and serum samples were analyzed using untargeted metabolomics. Gut microbial composition and diversity were assessed using α- and β-diversity indices, while Linear discriminant analysis effect size (LEfSe) identified differentially abundant taxa. Metabolomic pathway analysis was performed to detect significant changes in serum metabolites, and Spearman’s correlation was used to evaluate associations between gut microbes and metabolites. SCI significantly altered gut microbiota composition, with increased proportions of Ligilactobacillus and Staphylococcus, and decreased proportions of Lactobacillus and Limosilactobacillus. Metabolomic analysis revealed disrupted energy metabolism and elevated oxidative stress in SCI rats, as indicated by increased serum levels of pyruvate and lactic acid. Correlation analysis further identified significant associations between specific gut bacteria and key metabolites, suggesting microbiome-driven metabolic dysregulation following SCI. These findings highlight significant interactions between the gut microbiota and host metabolism after SCI and suggest that microbiome-targeted interventions may hold therapeutic potential for improving recovery by modulating metabolic function and oxidative stress responses.