Hyocholic acids shape neonatal immune tolerance and microbiota assembly
- David Ojcius
- Jun 3
- 1 min read
Highlights
HCAs dominate meconium (>50%) as primary bile acids produced by fetal CYP3A7
HCAs shape intestinal immune tolerance by promoting Treg cells and suppressing Th17 cells
High neonatal HCAs protect against gastrointestinal disorders and infections
Summary
Bile acids (BAs) are essential for regulating metabolism, immune responses, and host immunity-gut microbiome interactions. Here, we report that in human newborns, hyocholic acid (HCA) species constitute 51.03% of total BAs in meconium and 13.74% in infant serum, declining to <5% in adults. HCAs drive CD4+ 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.
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