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Dysregulation of bile acids increases the risk for preterm birth in pregnant women.


ABSTRACT: Preterm birth (PTB) is the leading cause of perinatal mortality and newborn complications. Bile acids are recognized as signaling molecules regulating a myriad of cellular and metabolic activities but have not been etiologically linked to PTB. In this study, a hospital-based cohort study with 36,755 pregnant women is conducted. We find that serum total bile acid levels directly correlate with the PTB rates regardless of the characteristics of the subjects and etiologies of liver disorders. Consistent with the findings from pregnant women, PTB is successfully reproduced in mice with liver injuries and dysregulated bile acids. More importantly, bile acids dose-dependently induce PTB with minimal hepatotoxicity. Furthermore, restoring bile acid homeostasis by farnesoid X receptor activation markedly reduces PTB and dramatically improves newborn survival rates. The findings thus establish an etiologic link between bile acids and PTB, and open an avenue for developing etiology-based therapies to prevent or delay PTB.

SUBMITTER: You S 

PROVIDER: S-EPMC7193585 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Dysregulation of bile acids increases the risk for preterm birth in pregnant women.

You Sangmin S   Cui Ai-Min AM   Hashmi Syed F SF   Zhang Xinmu X   Nadolny Christina C   Chen Yuan Y   Chen Qiwen Q   Bush Xin X   Hurd Zachary Z   Ali Winifer W   Qin Gang G   Deng Ruitang R  

Nature communications 20200430 1


Preterm birth (PTB) is the leading cause of perinatal mortality and newborn complications. Bile acids are recognized as signaling molecules regulating a myriad of cellular and metabolic activities but have not been etiologically linked to PTB. In this study, a hospital-based cohort study with 36,755 pregnant women is conducted. We find that serum total bile acid levels directly correlate with the PTB rates regardless of the characteristics of the subjects and etiologies of liver disorders. Consi  ...[more]

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