Table 1_Biliary microbiota and metabolic reprogramming in gallstone-associated gallbladder cancer: evidence from bile, stones, mucosa and tumor tissue.docx

This disparity has directed attention to the local conditions created by concentrated bile, stone surfaces, persistent microbes and altered bile acid and lipid metabolism. Evidence in this field is difficult to compare because bile, stones, mucosa and tumor tissue measure different biological processes, while human associations, animal experiments and cross-sectional omics studies are often discussed together.

We evaluated microbiological, metabolic and tissue-level studies according to the material examined, disease endpoint and study design, covering gallstone formation, chronic epithelial injury, preneoplastic lesions and established GBC. Salmonella is the most extensively studied microbial candidate, but epidemiological estimates vary with carrier prevalence, detection method and the use of gallstone controls. Fungal findings in GBC currently derive from one exploratory peptide-classification study, whereas separate fungal experiments concern gallstone formation.