Prevotella copri transplantation promotes neurorehabilitation in a mouse model of traumatic brain injury

Abstract

Abstract Background The gut microbiota plays a critical role in regulating brain function through the microbiome-gut-brain axis (MGBA). Dysbiosis of the gut microbiota is associated with neurological impairment in TBI patients. Our previous study found that TBI results in a decrease in the abundance of Prevotella copri (P. copri). Manipulation of the gut microbiota is a promising intervention strategy, but less is known about the potential role of P. copri transplantation in TBI. Methods In this study, a controlled cortical impact (CCI) model was used to induce traumatic brain injury (TBI) in adult male C57BL/6 mice. Subsequently, P. copri was transplanted by intragastric gavage for 7 consecutive days. To investigate the effect of the GUO-PI3K/Akt pathway in P. copri transplantation therapy, guanosine (GUO) was administered 2 h after TBI for 7 consecutive days, and PI3K inhibitor (LY294002) was administered 30 min before TBI. Various techniques were used to assess the effects of these interventions, including quantitative PCR, neurological behavior tests, metabolite analysis, ELISA, Western blot analysis, immunofluorescence, Evans blue assays, transmission electron microscopy, FITC-dextran permeability assay, gastrointestinal transit assessment, and 16S rDNA sequencing. Results P. copri abundance was significantly reduced after traumatic brain injury (TBI). P. copri transplantation alleviated motor and cognitive deficits tested by the NSS, Morris water maze, and open field test. P. copri transplantation attenuated oxidative stress and blood-brain barrier damage and reduced neuronal apoptosis after TBI. In addition, P. copri transplantation resulted in the reshaping of the intestinal flora, improved gastrointestinal motility and intestinal wall permeability. Metabolomics and ELISA analysis revealed a significant increase in GUO levels in feces, serum and injured brain after P. copri transplantation. Furthermore, the expression of p-PI3K and p-Akt was found to be increased after P. copri transplantation and GUO treatment. Notably, LY294002 treatment attenuated the observed improvements. Conclusions We demonstrate for the first time that P. copri transplantation can improve GI functions and alter gut microbiota dysbiosis after TBI. Additionally, P. copri transplantation can ameliorate neurological deficits, possibly via the GUO-PI3K/Akt signaling pathway after TBI.