Abstract
BACKGROUND: Cholestasis is characterized by disrupted bile flow and can lead to severe liver disease in newborns, of which biliary atresia (BA) is a common cause. The gut microbiome plays a crucial role in aggravating liver injury in BA and non-BA cholestasis. However, information is lacking regarding the differences in gut microbiome composition between patients with BA and non-BA cholestasis. PURPOSE: This study aimed to assess the gut microbiome profile of infants with BA versus those with non-BA cholestasis and healthy controls in an Indonesian population. METHODS: We investigated the changes in the microbial composition of fecal samples from 12 infants with BA and 8 with non-BA cholestasis and compared them with those of 8 age-matched healthy controls (HCs). Fecal DNA from all the participants was subjected to 16S rRNA amplicon sequencing. RESULTS: The fecal microbiome at the phylum level differed between the BA and non-BA cholestasis groups with increased Proteobacteria and decreased Firmicutes. At the genus level, the BA group was enriched with Bacteroides, unclassified Enterobacteriaceae, and Dialister (P<0.05), whereas the non-BA group was enriched with Klebsiella, Chryseobacterium, Acinetobacter, and Pseudomonas (P<0.05). Parabacteroides, unclassified Lachnospiraceae, Actinomyces, Anaerococcus, Clostridium innocuum group, Collinsella, Gemella, and Peptostreptococcaceae (P<0.05) were more enriched in the HC than in the other 2 groups. Detected cytomegalovirus in fecal samples was associated with significant microbial shifts, including increased Lactobacillus, decreased Escherichia-Shigella, and altered Faith's phylogenetic diversity, highlighting its potential role in gut microbiome modulation. Microbial alterations in patients with BA versus non-BA cholestasis were significantly correlated with liver function indicators. CONCLUSION: The BA and non-BA groups showed specific genus enrichment, highlighting the urgent need to identify potential treatments to inhibit the progression of liver injury in infants with cholestasis.