An integrated analysis of spinal cord transcriptome and gut microbiome unravel age-associated host-microbiome interactions following spinal cord injury

TL;DR

This study explores how aging affects spinal cord injury recovery by analyzing gene expression and gut microbiome changes in young and aged mice.

Contribution

The study reveals age-dependent shifts in gut microbiota and spinal cord inflammation following SCI, highlighting host-microbiome interactions.

Findings

Aging alters spinal cord gene expression after SCI, with immune and inflammatory pathways being most affected.

Aged mice show a greater decline in gut microbiota diversity, particularly in Lactobacillus and Dubosiella, during the chronic phase of SCI.

Changes in gut microbiota abundance correlate with variations in spinal cord inflammatory cytokine levels.

Abstract

Spinal cord injury (SCI) leads to irreversible neurological deficits, with emerging evidence highlighting the pivotal regulatory role of gut microbiota in neural repair through the bidirectional gut-brain axis. This study investigates age-related differences in SCI progression by longitudinally profiling multi-omics signatures in young versus aged mice, integrating spinal cord transcriptomics with gut microbiome analysis.

A traumatic SCI model was established at the thoracic level 10 in mice. The gut microbiota was analyzed through 16S rRNA sequencing. Spinal cord gene expression was profiled using transcriptome sequencing. Correlation analysis was performed to evaluate associated between gut microbiota shifts and differential cytokines expression.

Aging significantly altered spinal cord gene expression profiles after SCI, KEGG pathway analysis revealed that differentially expressed genes (DEGs) in young and aged SCI mice were highly similar, predominantly involving immune and inflammatory response pathways. The age-dependent upregulation of inflammatory cytokines were observed under both sham and post-SCI conditions. Additionally, aging was associated with distinct shifts in gut microbiota composition across different phases of SCI. The abundance of certain bacterial genera, such as Lactobacillus and Dubosiella, which was significantly reduced in the acute phase, continued to decline in an age-dependent manner during the chronic phase. Correlation analysis indicated that alterations in the abundance of the gut microbiota were closely associated with variations in spinal cord inflammatory cytokine levels.

This study delineates host-microbiome interactions in SCI and sheds light on potential mechanisms underlying age-related impairment of neural repair capacity.

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