A comprehensive review published in the World Journal of Pediatric Surgery highlights the gut microbiome as a critical factor in biliary atresia (BA), the leading cause of liver transplantation in children. The review, conducted by Dr. Vandana Jain and available at DOI: 10.1136/wjps-2025-001068, 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 corrective surgery and are strongly linked to poorer outcomes, including failure to clear jaundice and more rapid disease progression.
BA is a progressive fibro-obliterative disease of the bile ducts affecting 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. Despite decades of research and various post-surgical therapies—including antibiotics, bile acid medications, and steroids—the majority of patients still require liver transplantation by early adulthood.
The review reveals a remarkably consistent microbial signature in BA across multiple studies. Before surgery, infants show a pronounced shift in microbial composition compared to healthy babies, with pathobionts such as Streptococcus, Enterococcus, Veillonella, Klebsiella, and Clostridium dominating, while beneficial commensals like Bifidobacterium, Faecalibacterium, and Blautia are severely depleted. This pattern persists and worsens after the Kasai procedure, driven by ongoing cholestasis and clinical practices such as reduced breastfeeding rates and routine use of broad-spectrum prophylactic antibiotics. Critically, the depletion of Bifidobacterium has been linked to worse jaundice clearance, increased liver fibrosis, and a higher risk of post-surgical cholangitis—a serious complication that further damages the liver.
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. According to the authors, "The gut microbiome is not just a bystander in BA—it appears to be an active participant in disease progression."
These 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.
