Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Identification of a plant isoflavonoid that causes biliary atresia.

Authors: Lorent, Kristin; Gong, Weilong; Koo, Kyung A; Waisbourd-Zinman, Orith; Karjoo, Sara; Zhao, Xiao; Sealy, Ian; Kettleborough, Ross N; Stemple, Derek L; Windsor, Peter A; Whittaker, Stephen J; Porter, John R; Wells, Rebecca G; Pack, Michael

Published In Sci Transl Med, (2015 May 06)

Abstract: Biliary atresia (BA) is a rapidly progressive and destructive fibrotic disorder of unknown etiology affecting the extrahepatic biliary tree of neonates. Epidemiological studies suggest that an environmental factor, such as a virus or toxin, is the cause of the disease, although none have been definitively established. Several naturally occurring outbreaks of BA in Australian livestock have been associated with the ingestion of unusual plants by pregnant animals during drought conditions. We used a biliary secretion assay in zebrafish to isolate a previously undescribed isoflavonoid, biliatresone, from Dysphania species implicated in a recent BA outbreak. This compound caused selective destruction of the extrahepatic, but not intrahepatic, biliary system of larval zebrafish. A mutation that enhanced biliatresone toxicity mapped to a region of the zebrafish genome that has conserved synteny with an established human BA susceptibility locus. The toxin also caused loss of cilia in neonatal mouse extrahepatic cholangiocytes in culture and disrupted cell polarity and monolayer integrity in cholangiocyte spheroids. Together, these findings provide direct evidence that BA could be initiated by perinatal exposure to an environmental toxin.

PubMed ID: 25947162 Exiting the NIEHS site

MeSH Terms: Amaranthaceae/chemistry*; Animals; Australia; Biliary Atresia/etiology*; Biliary Atresia/pathology; Biliary Atresia/veterinary; Biological Assay; Cattle; Disease Models, Animal; Exome; Flavonoids/chemistry*; Genetic Predisposition to Disease; Humans; Immunity, Innate; Mice; Microscopy, Confocal; Mutation; Plant Extracts/chemistry*; Rats; Sheep; Zebrafish

to Top