biostudies-literatureZemmel ZMNICHD NIH HHSNIDDK NIH HHSNINDS NIH HHS2551879https://www.ebi.ac.uk/biostudies/studies/S-EPMC12416178biostudies-literatureUnknown17(1)The gut microbiome is an emerging factor in the neurobiology of disease. Blood-brain barrier (BBB) integrity is essential for proper brain function. However, the role the initial microbiome plays in BBB and brain development is unclear. In this study, we colonized germ-free pregnant mice with human full-term- or preterm-infant-derived gut microbiota, thereby establishing these communities in the resulting offspring. We discovered that mice harboring a full-term-associated microbiome exhibited stronger memory and learning capabilities and dramatically decreased early-life BBB permeability when compared to those with a prematurity-associated microbiome. Whole-brain single-cell RNA sequencing revealed downregulation of synaptic signaling genes in BBB cell types of mice with the prematurity-asGut microbesEarly-life gut microbiome maturity regulates blood-brain barrier and cognitive development.PMC12416178R21 NS121432R01 HD105234P30 DK042086Tsai HMLu LLittle JCFan XClaud ECLu JAndrews BRamaswamy RMarkiewicz EZemmel ZMYu YfalseEarly-life gut microbiome maturity regulates blood-brain barrier and cognitive development.The gut microbiome is an emerging factor in the neurobiology of disease. Blood-brain barrier (BBB) integrity is essential for proper brain function. However, the role the initial microbiome plays in BBB and brain development is unclear. In this study, we colonized germ-free pregnant mice with human full-term- or preterm-infant-derived gut microbiota, thereby establishing these communities in the resulting offspring. We discovered that mice harboring a full-term-associated microbiome exhibited stronger memory and learning capabilities and dramatically decreased early-life BBB permeability when compared to those with a prematurity-associated microbiome. Whole-brain single-cell RNA sequencing revealed downregulation of synaptic signaling genes in BBB cell types of mice with the prematurity-as2025-01-01T00:00:00Z2025 Dec2026-06-03T05:59:05.723Z2026-04-25T03:18:59.677ZS-EPMC124161784088615210.1080/19490976.2025.2551879