Hyocholic acids shape neonatal immune tolerance and microbiota assembly

T cell differentiation toward regulatory T cells while suppressing pro-inflammatory T helper (Th)17 cells, facilitating healthy microbiome colonization. Neonates with high HCA levels show a reduced incidence of infections and gastrointestinal disorders during the first year of life. Mechanistically, HCAs are produced by the fetal-specific enzyme CYP3A7, creating a transient metabolic window that coordinates the gut-immune axis during early development. These findings reveal HCAs as primary BAs and critical mediators of immune programming, with implications for preventing early-life inflammatory diseases.