The study investigates the influence of gut microbiota on blood-brain barrier (BBB) permeability in mice. Key findings include: 1. **Germ-Free Mice Show Increased BBB Permeability**: Germ-free mice, reared from intrauterine life without exposure to live bacteria, exhibit increased BBB permeability compared to pathogen-free mice with normal gut flora. This increased permeability is maintained throughout adulthood and is associated with reduced expression of tight junction proteins (occludin and claudin-5). 2. **Maternal Gut Microbiota Influences BBB Development**: In utero, germ-free mice show altered BBB permeability compared to pathogen-free mice, with a shift from diffuse to localized BBB permeability around E15.5 to E17.5. 3. **BBB Permeability and Gut Microbiota**: Colonization of germ-free adult mice with pathogen-free gut flora or treatment with bacterial metabolites (sodium butyrate) reduces BBB permeability and increases tight junction protein expression (occludin and claudin-5). 4. **SCFAs and BBB Integrity**: Short-chain fatty acids (SCFAs) produced by gut bacteria, such as butyrate, acetate, and propionate, affect BBB permeability. Treatment with these SCFAs or specific bacterial strains (e.g., *Clostridium tyrobutyricum*) in germ-free mice improves BBB integrity. 5. **Discussion**: The study highlights the role of gut microbiota in maintaining BBB integrity, suggesting that changes in gut microbiota can influence BBB function and potentially impact brain development and health. The findings provide insights into the complex interactions between the gut microbiota and the brain, emphasizing the importance of a healthy gut microbiota for brain health.The study investigates the influence of gut microbiota on blood-brain barrier (BBB) permeability in mice. Key findings include: 1. **Germ-Free Mice Show Increased BBB Permeability**: Germ-free mice, reared from intrauterine life without exposure to live bacteria, exhibit increased BBB permeability compared to pathogen-free mice with normal gut flora. This increased permeability is maintained throughout adulthood and is associated with reduced expression of tight junction proteins (occludin and claudin-5). 2. **Maternal Gut Microbiota Influences BBB Development**: In utero, germ-free mice show altered BBB permeability compared to pathogen-free mice, with a shift from diffuse to localized BBB permeability around E15.5 to E17.5. 3. **BBB Permeability and Gut Microbiota**: Colonization of germ-free adult mice with pathogen-free gut flora or treatment with bacterial metabolites (sodium butyrate) reduces BBB permeability and increases tight junction protein expression (occludin and claudin-5). 4. **SCFAs and BBB Integrity**: Short-chain fatty acids (SCFAs) produced by gut bacteria, such as butyrate, acetate, and propionate, affect BBB permeability. Treatment with these SCFAs or specific bacterial strains (e.g., *Clostridium tyrobutyricum*) in germ-free mice improves BBB integrity. 5. **Discussion**: The study highlights the role of gut microbiota in maintaining BBB integrity, suggesting that changes in gut microbiota can influence BBB function and potentially impact brain development and health. The findings provide insights into the complex interactions between the gut microbiota and the brain, emphasizing the importance of a healthy gut microbiota for brain health.