# Cross-country multi-modal evidence links Aspergillus to biliary atresia

## TL;DR

This study suggests a possible link between gut fungi, specifically Aspergillus, and biliary atresia in infants, based on multi-country data and case evidence.

## Contribution

The study presents cross-country multi-modal evidence linking Aspergillus in the gut to biliary atresia, a novel hypothesis in pediatric liver disease.

## Key findings

- Gut Aspergillus was detected only in biliary atresia cases, suggesting it may be a trigger.
- BA incidence correlated with Aspergillus infections in the UK, Taiwan, and Japan.
- Antifungal treatment resolved cholangitis in a BA case, supporting the hypothesis.

## Abstract

Biliary atresia (BA) is the leading cause of pediatric liver transplantation. It is characterized by progressive extrahepatic bile duct obstruction in young infants. Inspired by the success of antifungal treatment in a newborn with BA-related obstructive cholangitis, we explored a potential link between BA and fungi, particularly Aspergillus. Fecal DNA was analyzed using 18S ribosomal sequencing and validated with a published fecal metagenomic dataset. Epidemiological data from the UK, Taiwan, and Japan were also examined.

Gut Aspergillus was exclusively detected in BA cases, suggesting it may be a potential trigger. Independent fecal metagenomic data from China and epidemiological correlations further supported this hypothesis. In the UK, BA presentations strongly correlated (r = 0.98, 95% CI [0.36, 1.0], p = 0.02) with Aspergillosis, but not with Candidiasis, during the COVID-19 lockdown. In Taiwan, a decade of data showed BA incidence was significantly associated (r = 0.78, 95% CI [0.29, 0.94], p = 0.01) with yearly Aspergillus-positive isolates among cancer-adjusted hospital admissions. In Japan, BA cases over 25 years correlated significantly (r = 0.85, 95% CI [0.37, 0.97], p = 0.01) with visceral Aspergillus burdens in autopsied cases, but not with other fungal infections.

The resolution of obstructive cholangitis in the antifungal-treated index case, together with multi-modal, cross-country evidence, highlights a potential link between gut Aspergillus and BA. Although limited by small sample size, retrospective design, and lack of mechanistic validation, the study may still be interpreted as hypothesis-generating and underscores the need for prospective studies to validate and extend these observations.

The online version contains supplementary material available at 10.1186/s13099-025-00772-7.