Xiaojiao Zheng, Jieyi Wang, Yimin Sun, Huiheng Zhang, Yajun Tang, Junliang Kuang, Fuxin Jiao, Chuhui Zhou, Mengyu Xia, Jiaqin Ren, Yu Cai, Changliang Yao, Aihua Zhao, Chun Qu, Lu Liu, Yifan Yang, Qifei Guan, Rongzhen Jiang, Zhenxing Ren, Tianlu Chen, Mengci Li, Xixi Xia, Linyu Xia, Mingliang Zhao, Yang Li, Keke Ding, Zile Zhou, Yan Shi, Xinjian Wan, Beicheng Sun, Guoxiang Xie, Fei Gao, Zhou, Jian, 1971-, Cheng Hu, Yan He, Weiping Jia, Ri-hua Xie, Wei Jia
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.