Microbiota differences between commercial breeders impacts the post-stroke immune response.

Area of Science:

• Neuroscience
• Immunology
• Microbiology

Background:

• Experimental reproducibility is hindered by inter-laboratory variations, especially in immunomodulatory therapy studies for brain diseases.
• The gut microbiota influences immune cell polarization and has shown efficacy in treating various brain disorders.

Purpose of the Study:

• To investigate the impact of gut microbiota differences between mice from different commercial breeders on the post-stroke neuroinflammatory response.
• To assess the correlation between specific microbiota compositions and immune responses, particularly T cell polarization, in mice with ischemic stroke.

Main Methods:

• Compared microbiota composition and diversity in C57BL/6 mice from three commercial breeders.
• Investigated the presence of segmented filamentous bacteria (SFB) and their correlation with Treg/Th17 cell ratios.
• Assessed the effects of SFB recolonization and CD28 superagonist (CD28SA) treatment on T cell populations and stroke outcomes.

Main Results:

• Substantial differences in microbiota composition, including the presence/absence of SFB, were found between breeders.
• SFB presence correlated with specific Treg/Th17 cell ratios, and SFB recolonization shifted these ratios.
• CD28SA treatment efficacy varied between breeders and was impaired in SFB-free mice, leading to larger brain infarcts in SFB-lacking mice.

Conclusions:

• Gut microbiota composition, specifically SFB presence, significantly influences T cell polarization during ischemic stroke.
• Microbiota variations impact the effectiveness of immunomodulatory therapies like CD28SA.
• Inter-laboratory differences in mouse microbiota can profoundly affect experimental outcomes and translational research in brain disease.