Hyocholic acids shape neonatal immune tolerance and microbiota assembly

Area of Science:

• Immunology
• Metabolism
• Microbiome Research

Background:

• Bile acids (BAs) are vital for metabolism, immune responses, and gut microbiome interactions.
• The role of specific BAs in early human development and immune programming is not fully understood.

Purpose of the Study:

• To investigate the role of hyocholic acids (HCAs) in human newborns and their impact on immune development and health.
• To elucidate the mechanism of HCA production and its function in coordinating the gut-immune axis.

Main Methods:

• Quantification of BA composition in meconium, infant serum, and adult serum.
• Analysis of HCA effects on CD4+ T cell differentiation (T regulatory cells and T helper 17 cells).
• Correlation analysis between HCA levels and incidence of infections and gastrointestinal disorders in neonates.

Main Results:

• Hyocholic acid (HCA) species are abundant in human newborns (51.03% in meconium, 13.74% in infant serum), decreasing significantly in adults (<5%).
• HCAs promote regulatory T cell differentiation and suppress T helper 17 cells, aiding microbiome colonization.
• Elevated neonatal HCA levels are associated with reduced incidence of early-life infections and gastrointestinal disorders.
• The fetal-specific enzyme CYP3A7 produces HCAs, establishing a transient metabolic window for gut-immune axis coordination.

Conclusions:

• Hyocholic acids are primary bile acids in newborns, acting as critical mediators of immune programming.
• HCA-mediated immune modulation facilitates healthy microbiome colonization and reduces susceptibility to early-life inflammatory diseases.
• Targeting the HCA metabolic window may offer strategies for preventing inflammatory conditions in early life.