A comprehensive review published in the World Journal of Pediatric Surgery highlights the gut microbiome as a critical factor in the progression of biliary atresia (BA), the leading cause of liver transplantation in children. The review, conducted by Dr. Vandana Jain, synthesizes evidence showing that infants with BA harbor a severely imbalanced gut microbial ecosystem, characterized by an overgrowth of harmful bacteria and a depletion of beneficial microbes like Bifidobacterium. These disturbances are present before surgery and are strongly linked to poorer outcomes, including failure to clear jaundice and more rapid disease progression.
Biliary atresia is a progressive fibro-obliterative disease of the bile ducts that affects approximately one in 10,000 to 15,000 infants worldwide. The standard surgical intervention, the Kasai portoenterostomy, aims to restore bile drainage by connecting the liver directly to the small intestine. However, only about 60% of infants achieve adequate bile flow, and ongoing liver injury often persists, leading to liver transplantation by early adulthood for most patients. Despite decades of research and various post-surgical therapies, including antibiotics, bile acid medications, and steroids, outcomes remain poor. The gut microbiome has emerged as a major player in liver diseases, but its role in neonatal and infant liver conditions has remained largely unexplored.
The review, published on January 7, 2026, with DOI 10.1136/wjps-2025-001068, examines microbial composition in patients before and after the Kasai procedure. It identifies consistent patterns of dysbiosis, including a shift toward pathobionts such as Streptococcus, Enterococcus, Veillonella, Klebsiella, and Clostridium, while beneficial commensals like Bifidobacterium, Faecalibacterium, and Blautia are severely depleted. This pattern persists and worsens after surgery, driven by ongoing cholestasis, reduced breastfeeding rates, and the routine use of broad-spectrum prophylactic antibiotics, which suppress beneficial bacteria. Critically, the depletion of Bifidobacterium has been linked to worse jaundice clearance, increased liver fibrosis, and a higher risk of post-surgical cholangitis.
The review also highlights emerging evidence that microbial metabolites, particularly short-chain fatty acids like acetate and butyrate, may play protective roles, with butyrate showing potential anti-fibrotic effects in experimental models. Disruptions in bile acid metabolism, driven by gut bacteria through enzymes like bile salt hydrolase, further compound the problem, creating a vicious cycle of liver injury and microbial imbalance. "The gut microbiome is not just a bystander in BA — it appears to be an active participant in disease progression," the authors said. "We're seeing consistent patterns where harmful bacteria expand and beneficial ones like Bifidobacterium are lost, and these changes correlate with how well patients do after surgery. The exciting part is that the microbiome is modifiable."
The findings open the door to new therapeutic approaches for BA, where treatment options have remained limited for decades. Microbiome-modulating strategies — including probiotics, prebiotics, and potentially fecal microbiota transplantation — have shown promise in adult liver diseases and could be adapted for infants. Early studies with Lactobacillus rhamnosus GG have yielded mixed results, suggesting that strain selection, timing, and combination approaches will be critical. The review also calls for a re-evaluation of current clinical practices, such as the widespread use of prophylactic antibiotics immediately after the Kasai procedure, which may inadvertently disrupt the developing microbiome. By integrating microbiome science into clinical care, researchers hope to improve native liver survival and reduce the need for liver transplantation in these vulnerable infants.
