The gut microbiota could play a bigger role in the development of liver and biliary diseases such as primary biliary cholangitis (PBC) than was previously thought, according to a recently published study in the journal Microorganisms.
The gut microbiota is a broad term that describes the millions of bacteria that inhabit our intestines. Increasing research shows that these bacteria play an important role in digestion, immune regulation and hormonal regulation.
Historically believed to be sterile, the biliary tract is now known to host small but functionally significant microbial communities. These microbes can contribute to the development and progression of both benign and malignant biliary diseases, especially under stress conditions.
“The evidence amassed over the past decade converges on a fundamental paradigm shift: neither the biliary tract nor the pancreatic parenchyma is intrinsically sterile,” the authors wrote. “Instead, each hosts low-biomass but metabolically active microbial communities that engage in continuous crosstalk with epithelial, immune and stromal compartments, modulate bile acid pools, and, when dysbiotic, precipitate chronic inflammation, fibrosis, and tumorigenesis,”
The authors aimed to explore how microbial landscapes influence bile duct disorders, liver malignancies and gallbladder cancer through an extensive review. The objective was to shed light on their mechanisms and potential therapeutic implications.
The authors noted that under healthy conditions, the biliary environment is protected by multiple barriers, including bile flow, mucosal immunity and antimicrobial proteins.
However, disruptions such as biliary stenting or disease-related obstructions can break these defenses, allowing colonization by microbes such as Enterococcus faecalis and Streptococcus. These bacteria are capable of metabolizing bile acids into toxic compounds and have been associated with chronic inflammation and fibrosis, especially in autoimmune liver diseases.
The authors observed that people with primary sclerosing cholangitis (PSC) — like PBC, a disease impacting the bile ducts — exhibit reduced microbial diversity and increased levels of bacteria like Veillonella and Enterococcus, particularly strains correlated with elevated levels of cell-toxic bile acids. These changes promote blood vessel injury, immune activation and scarring. Limited studies on the biliary microbiome in PSC suggest that a dysbiotic microbial environment may also drive disease progression and even malignant transformation in advanced stages.
In PBC, gut microbiome alterations, such as reduced Faecalibacterium and increased pro-inflammatory taxa like Veillonella and Klebsiella, have been linked to poorer response to ursodeoxycholic acid (UDCA). Biliary microbiome studies in PBC remain scarce, but existing data suggest the presence of Gram-positive cocci, such as Staphylococcus aureus and Enterococcus faecium, particularly in advanced disease stages.
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