Biliatresone: progress in biliary atresia study

Biliary atresia (BA) is one of the main causes of neonatal end-stage liver disease. Without timely diagnosis and treatment, most children with BA will develop irreversible liver fibrosis within the first two months. While current theorized causes of BA include viral infection, immune disorders, and genetic defects, the comprehensive etiology is still largely unknown. Recently, biliatresone attracted much interest for its ability to induce BA in both zebrafish and mice, so we summarized the latest progress of biliatresone research in BA and tried to answer the question of whether it could provide further clues to the etiology of human BA.We conducted a PubMed search for any published articles related to the topic using search terms including "biliary atresia", "biliatresone", "GSH", and "HSP90". Relevant data were extracted from the original text or supplementary materials of the corresponding articles.Biliatresone had shown its unique toxicity in multiple species such as zebrafish and mice, and pathogenic factors involved included glutathione (GSH), heat shock protein 90 (HSP90) and the related pathways. In combination with epidemiological evidence and recent studies on the intestinal flora in biliary atresia, a new pathogenic hypothesis that the occurrence of biliary atresia is partly due to biliatresone or its structure-like compounds depositing in human body via vegetables or/and the altered intestinal flora structure can be tentatively established.Based on the existing evidence, we emphasized that GSH and HSP90 are involved in the development of BA, and the maternal diet, especially higher vegetable intake of Asian women of childbearing age, accompanied by the altered intestinal flora structure, may contribute to the occurrence of biliary atresia and the higher incidence in the Asia group. However, the evidence from large sample epidemiological research is necessary.