Hyocholic acids shape neonatal immune tolerance and microbiota assembly.
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- Record sourced from PubMed, PMID 42167251.
- Also identified by DOI 10.1016/j.cmet.2026.04.016.
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Abstract
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<sup>+</sup> 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.