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bioRxiv · 10.1101/2024.04.01.587652

Probiotic treatment causes sex-specific neuroprotection after traumatic brain injury in mice

Holcomb, M.·Marshall, A.·Flinn, H.·Lozano, M.·Soriano, S.·Gomez-Pinilla, F.·Treangen, T.·Villapol, S.
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Abstract

BackgroundRecent studies have shed light on the potential role of gut dysbiosis in shaping traumatic brain injury (TBI) outcomes. Changes in the levels and types of Lactobacillus bacteria present might impact the immune system disturbances, neuroinflammatory responses, anxiety and depressive-like behaviors, and compromised neuroprotection mechanisms triggered by TBI. ObjectiveThis study aimed to investigate the effects of a daily pan-probiotic (PP) mixture in drinking water containing strains of Lactobacillus plantarum, L. reuteri, L. helveticus, L. fermentum, L. rhamnosus, L. gasseri, and L. casei, administered for either two or seven weeks before inducing TBI on both male and female mice. MethodsMice were subjected to controlled cortical impact (CCI) injury. Short-chain fatty acids (SCFAs) analysis was performed for metabolite measurements. The taxonomic profiles of murine fecal samples were evaluated using 16S rRNA V1-V3 sequencing analysis. Histological analyses were used to assess neuroinflammation and gut changes post-TBI, while behavioral tests were conducted to evaluate sensorimotor and cognitive functions. ResultsOur findings suggest that PP administration modulates the diversity and composition of the microbiome and increases the levels of SCFAs in a sex-dependent manner. We also observed a reduction of lesion volume, cell death, and microglial and macrophage activation after PP treatment following TBI in male mice. Furthermore, PP-treated mice show motor function improvements and decreases in anxiety and depressive-like behaviors. ConclusionOur findings suggest that PP administration can mitigate neuroinflammation and ameliorate motor and anxiety and depressive-like behavior deficits following TBI. These results underscore the potential of probiotic interventions as a viable therapeutic strategy to address TBI-induced impairments, emphasizing the need for gender-specific treatment approaches.

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Holcomb, M., Marshall, A., Flinn, H., Lozano, M., Soriano, S., Gomez-Pinilla, F., Treangen, T., Villapol, S.. 2024-04-02. Probiotic treatment causes sex-specific neuroprotection after traumatic brain injury in mice. https://doi.org/10.1101/2024.04.01.587652

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