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Publication : Gut microbiota alters host bile acid metabolism to contribute to intrahepatic cholestasis of pregnancy.

First Author  Tang B Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  1305
PubMed ID  36894566 Mgi Jnum  J:335706
Mgi Id  MGI:7443643 Doi  10.1038/s41467-023-36981-4
Citation  Tang B, et al. (2023) Gut microbiota alters host bile acid metabolism to contribute to intrahepatic cholestasis of pregnancy. Nat Commun 14(1):1305
abstractText  Intrahepatic cholestasis of pregnancy (ICP) is a female pregnancy-specific disorder that is characterized by increased serum bile acid and adverse fetal outcomes. The aetiology and mechanism of ICP are poorly understood; thus, existing therapies have been largely empiric. Here we show that the gut microbiome differed significantly between individuals with ICP and healthy pregnant women, and that colonization with gut microbiome from ICP patients was sufficient to induce cholestasis in mice. The gut microbiomes of ICP patients were primarily characterized by Bacteroides fragilis (B. fragilis), and B. fragilis was able to promote ICP by inhibiting FXR signaling via its BSH activity to modulate bile acid metabolism. B. fragilis-mediated FXR signaling inhibition was responsible for excessive bile acid synthesis and interrupted hepatic bile excretion to ultimately promote the initiation of ICP. We propose that modulation of the gut microbiota-bile acid-FXR axis may be of value for ICP treatment.
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