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肠道微生物群在大鼠脊髓损伤恢复中作用的宏基因组学和代谢组学分析

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

作者信息

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

机构信息

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.

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.

出版信息

Biomol Biomed. 2025 Aug 5;25(9):2114-2126. doi: 10.17305/bb.2025.12164.

DOI:10.17305/bb.2025.12164
PMID:40169141
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.

摘要

脊髓损伤(SCI)会引发深刻的全身变化,包括肠道微生物群组成和宿主代谢的紊乱。本研究旨在调查SCI对大鼠肠道微生物多样性和血清代谢物的影响,并探索可能影响恢复的潜在微生物群-代谢物相互作用。将雄性Sprague-Dawley(SD)大鼠分为SCI组或假手术组。收集粪便样本进行全基因组宏基因组测序,并使用非靶向代谢组学分析血清样本。使用α-和β-多样性指数评估肠道微生物组成和多样性,而线性判别分析效应大小(LEfSe)确定差异丰富的分类群。进行代谢组学通路分析以检测血清代谢物的显著变化,并使用Spearman相关性评估肠道微生物与代谢物之间的关联。SCI显著改变了肠道微生物群组成,Ligilactobacillus和葡萄球菌的比例增加,而乳酸杆菌和Limosilactobacillus的比例降低。代谢组学分析显示,SCI大鼠的能量代谢紊乱和氧化应激升高,血清丙酮酸和乳酸水平升高表明了这一点。相关性分析进一步确定了特定肠道细菌与关键代谢物之间的显著关联,表明SCI后微生物群驱动的代谢失调。这些发现突出了SCI后肠道微生物群与宿主代谢之间的显著相互作用,并表明以微生物群为靶点的干预措施可能具有通过调节代谢功能和氧化应激反应来改善恢复的治疗潜力。

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引用本文的文献

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The Utility of Metabolomics in Spinal Cord Injury: Opportunities for Biomarker Discovery and Neuroprotection.代谢组学在脊髓损伤中的应用:生物标志物发现与神经保护的机遇
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