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

Sangmin You, Ai-Min Cui, Syed F. Hashmi, Xinmu Zhang, Christina Nadolny, Yuan Chen, Qiwen Chen, Xin Bush, Zachary Hurd, Winifer Ali, Gang Qin and Ruitang Deng ()
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Sangmin You: University of Rhode Island
Ai-Min Cui: Nantong University
Syed F. Hashmi: University of Rhode Island
Xinmu Zhang: University of Rhode Island
Christina Nadolny: University of Rhode Island
Yuan Chen: University of Rhode Island
Qiwen Chen: University of Rhode Island
Xin Bush: University of Rhode Island
Zachary Hurd: University of Rhode Island
Winifer Ali: University of Rhode Island
Gang Qin: Nantong University
Ruitang Deng: University of Rhode Island

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15923-4

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