Objectives: Recent evidence suggests that there is a link between gut and brain via microbial, immune, endocrine and neural signaling pathways, but the changes of gut-brain axis following brain trauma has not yet been clearly shown. The aim of this study was to reveal the gut microbiota and transcriptomic profile of the cerebral cortex in traumatic brain injury (TBI) mice.

Methods: A controlled cortical impact (CCI) device was used to establish a TBI model. Behavioral testing and histopathological analysis were performed. The gut microbiota was analyzed by 16S rRNA sequencing, and gene expression in the cerebral cortex was detected by whole-transcriptome sequencing (RNA-Seq) 7 days after TBI.

Results: The analysis of 16S rRNA sequencing data indicated that TBI increased the relative abundance of Bifidobacterium. The TBI group showed a disturbance in intestinal flora. RNA-Seq analysis identified 523 differentially expressed genes (481 upregulated and 42 downregulated) in the cerebral cortex of the TBI group compared with the sham group. Cluster analysis revealed 93 immune system process-related genes and 55 inflammatory response-related genes that were differentially expressed.

Conclusions: This manuscript reports pathogenic changes via the gut-brain axis driven by TBI, which confer persistent symptoms and susceptibility to neurodegeneration.