Hyocholic acids shape neonatal immune tolerance and microbiota assembly

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.

Read full article at:
https://www.sciencedirect.com/science/article/pii/S1550413126001543



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