Biliary microbiota and mucin 4 impact the calcification of cholesterol gallstones

Background:Cholesterol gallstones account for over 80%of gallstones,and the pathogenesis of gallstone formation involves genetic and environmental factors.However,data on the evolution of cholesterol gallstones with various densities are limited.This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis.Methods:Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones.The relative abundance of microbiota in gallbladder tissues was detected.Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1,MUC2,MUC3a,MUC3b,MUC4,MUC5ac and MUC5b in gallbladder tissues and bile.The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression.Results:A total of 23 patients with gallbladder stones were included.The density of gallstones in the isodense group was significantly lower than that of the calcified group(34.20±1.50 vs.109.40±3.84 HU,P<0.0001).Compared to the isodense group,the calcified group showed a higher abundance of gram-positive bacteria at the fundus,in the body and neck of gallbladder tissues.The concentrations of MUC1,MUC2,MUC3a,MUC3b,MUC5ac and MUC5b in the epithelial cells of gallbladder tissues showed no difference between the two groups,while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus(15.49±0.69 vs.10.23±0.54 ng/mL,P<0.05),in the body(14.54±0.94 vs.11.87±0.85 ng/mL,P<0.05)as well as in the neck(14.77±1.04 vs.10.85±0.72 ng/mL,P<0.05)of gallbladder tissues.Moreover,the abundance of bacteria was positively correlated with the expression of MUC4(r=0.569,P<0.05)in the calcified group.Conclusions:This study showed the potential clinical relevance among biliary microbiota,mucins and calcified gallstones in patients with gallstones.Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones.

Overexpression of sterol carrier protein-2 mRNA in patients with cholesterol gallstones

BACKGROUND: Hypersecretion of biliary cholesterol is believed to be one of the important causes of lithogenic bile. Sterol carrier protein-2 ( SCP2 ) participates in choles- terol trafficking and metabolism and may play a key role in cholesterol gallstone formation. This study was undertaken to investigate the expression of liver SCP2 mRNA in pa- tients with cholesterol gallstone and those patients with non-cholesterol gallstone. METHODS: The expression of liver SCP2 mRNA was studi- ed in 36 patients with cholesterol gallstone and 30 patients with non-cholesterol gallstone by reverse transcription-poly- merase chain reaction (RT-PCR). RESULT: The expression of SCP2 mRNA was increased more significantly in patients with cholesterol gallstone than in patients with non-cholesterol gallstone. CONCLUSION: The SCP2 gene was overexpressed in pa- tients with cholesterol gallstone, indicating that SCP2 may be one of the important causes of cholesterol gallstone.

Effect of intestinal transit on the formation of cholesterol gallstones in hamsters

BACKGROUND: The effect of 'intestinal transit' has become a new field of interest in the study of the pathogenesis of cholesterol gallstones. This study was undertaken to further test this notion and ascertain the relationship between impaired intestinal transit function and cholesterol gallstones. METHODS: A total of 64 hamsters were divided into 2 groups, experimental and control. Each was subdivided into 4 subgroups for sacrifice at different time. A high-cholesterol diet and a standard diet were fed to each group. The geometric center, which represents the intestinal transit function was calculated. RESULTS: The growth of all hamsters was normal. Cholesterol gallstones were found in 2 hamsters at the end of the 4th week. The geometric center values for the experimental and control groups were 2.3891 +/- 0.3923 vs. 2.7730 +/- 0.5283, at the end of week 3; 1.8148 +/- 0.4312 vs. 3.2294 +/- 1.1613 at week 4; 1.8451 +/- 0.3700 vs. 2.9075 +/- 0.3756 at week 5; and 1.8025 +/- 0.3413 vs. 3.0920 +/- 0.5622 at week 6. CONCLUSION: A high cholesterol diet can significantly reduce the intestinal transit function and facilitate the formation of cholesterol gallstones.

Research progress on the immune microenvironment of the gallbladder in patients with cholesterol gallstones

Cholesterol gallstones are very common in hepatobiliary surgery and have been studied to a certain extent by doctors worldwide for decades.However,the mechanism of cholesterol gallstone formation is not fully understood,so there is currently no completely effective drug for the treatment and prevention of cholesterol gallstones.The formation and development of cholesterol gallstones are caused by a variety of genetic and environmental factors,among which genetic susceptibility,intestinal microflora disorders,impaired gallbladder motility,and immune disorders are important in the pathogenesis of cholesterol gallstones.This review focuses on recent advances in these mechanisms.We also discuss some new targets that may be effective in the treatment and prevention of cholesterol gallstones,which may be hot areas in the future.

Cholesterol gallstones:Focusing on the role of interstitial Cajal-like cells

with a complex and multifactorial etiology.Declined gallbladder motility reportedly contributes to CG pathogenesis.Furthermore,interstitial Cajal-like cells(ICLCs)are reportedly present in human and guinea pig gallbladder tissue.ICLCs potentially contribute to the regulation of gallbladder motility,and aberrant conditions involving the loss of ICLCs and/or a reduction in its pacing potential and reactivity to cholecystokinin may promote CG pathogenesis.This review discusses the association between ICLCs and CG pathogenesis and provides a basis for further studies on the functions of ICLCs and the etiologies of CG.

Bile acids in serum and bile of patients with cholesterol gallstone

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Gastrointestinal microbiome and cholelithiasis:Current status and perspectives

Cholelithiasis is a common digestive disease affecting 10%to 15%of adults.It imposes significant global health and financial burdens.However,the pathogenesis of cholelithiasis involves several factors and is incompletely elucidated.In addition to genetic predisposition and hepatic hypersecretion,the pathogenesis of cholelithiasis might involve the gastrointestinal(GI)microbiome,consisting of microorganisms and their metabolites.High-throughput sequencing studies have elucidated the role of bile,gallstones,and the fecal microbiome in cholelithiasis,associating microbiota dysbiosis with gallstone formation.The GI microbiome may drive cholelithogenesis by regulating bile acid metabolism and related signaling pathways.This review examines the literature implicating the GI microbiome in cholelithiasis,specifically gallbladder stones,choledocholithiasis,and asymptomatic gallstones.We also discuss alterations of the GI microbiome and its influence on cholelithogenesis.