Project description:Gallstone disease is a worldwide common disease. However, the knowledges concerning the gallbladder in the pathogenesis of cholesterol gallstone formation remains limited. In this study, using single-cell RNA sequencing (scRNA-seq), we showed cellular heterogeneity and transcriptomic dynamics in murine gallbladder cells during the process of lithogenesis. Our results indicated gallbladder wall were subjected to remodeling during the process of lithogenesis. The major molecular events happened included proliferation of epithelial cells, infiltration of immune-cells, activation of angionesis and extracellular matrix modulation. Furthermore, we observed partial reversal of gallbladder cell transcriptomes by ursodeoxycholic acid treatment. This work thus provides novel and integral knowledges on the cellular changes during lithogenesis, which is of great significance to the understanding of pathogenesis and treatment of cholesterol gallstone.
Project description:Following a large-scale genome-wide association study of gallstone disease, we performed RNA sequencing from tissues of four human gallbladders (3 healthy controls and 1 case with chronic gallstones) and one liver sample from the gallstone case. We aimed to determine the expression patterns of gallstone disease-associated genes in gallbladder and liver, two organs of interest in disease etiology.
Project description:Cholesterol gallstone is a common disease, but the pathogenesis of gallstone remains a mystery. The pathogenetic factors of gallstone disease include a genetic background, cholesterol condensation and bile supersaturation, while the risk factors may include fatty liver, diabetes, obesity and microbiome dysbiosis. Dysbiosis refers to altered bacterial composition and abundance, which is found to be associated with the pathogenesis of variety of diseases. Mass spectrometry-based proteomics emerges as a powerful tool to identify protein expressions of human samples. A number of proteomic studies have been performed to analyze human protein contents of bile samples. All these studies focus on the analysis of human proteins, and no study to date has been performed to analyze the protein expression of microbiome in bile samples associated with gallstone disease. In current study, we performed a label-free metaproteomic analysis of gallbladder bile samples from cholesterol gallstone disease patients and normal individuals. Maxquant was used in the comprehensive database searching to infer protein groups with quantitation. We attempt to investigate the dysbiosis changes, potential virulence factor of microbiome and host immune responses which contribute to gallstone formation and cholelithiasis.
Project description:<p><strong>INTRODUCTION:</strong> Cholesterol gallstone (CGS) is a biliary tract disorder requiring treatment in approximately 20% of patients. The efficacy of Chaihu Shugan in preventing CGS recurrence after successful treatment remains uncertain.</p><p><strong>METHODS:</strong> We examined the <em>in vivo</em> preventive efficacy of Chaihu Shugan using a CGS mouse model and used multi-omics to study the interplay between gut microbiota, metabolism and gene expression.</p><p><strong>RESULTS:</strong> The intestinal microbiota was severely dysregulated during the formation of CGS, showing a marked decrease in the abundance of beneficial microbiota, especially <em>Lactobacillus</em> and <em>Akkermansia</em>. Chaihu Shugan prevented CGS formation by restoring the composition of the gut microbiota and reversing the metabolic disturbances caused by dysbiosis. This preventive effect of Chaihu Shugan was paralleled by changes in the expression of metabolism-related genes in the liver. A network pharmacology analysis of Chaihu Shugan revealed that obacunone may be the key active metabolite in regulating bile acid metabolism. Multi-omics and correlation analyses elucidated the interplay between gut microbiota, metabolism and gene alterations in the dosedependent effect of Chaihu Shugan.</p><p><strong>CONCLUSION:</strong> Our data show that Chaihu Shugan can prevent CGS and indicate its mechanisms of action.</p>
Project description:To explore the changes in the composition and diversity of intestinal microbiota during 3-weeks of modified MAC diet and conventional diet in stage I or low-risk stage II colorectal cancer (CRC) patients after surgery. Additionally, the investigator analyze the association of gut microbiota and stool formation pattern or quality of life according to dietary pattern. Therefore, the investigator identify the beneficial or harmful microbiota composition and diversity adapting modified MAC diet that related to cancer recurrence, which provide supporting evidence for future prospective trial.
Project description:<p>Gallstones are crystalline deposits in the gallbladder that are traditionally classified as cholesterol, pigment or mixed stones based on their composition. Microbiota and host metabolism variances among the different types of gallstones remain largely unclear. Here, the bile and gallstone microbial species spectra of 29 subjects with gallstone disease (GSD, 24 cholesterol and 5 pigment) were revealed by type IIB restriction site-associated DNA microbiome sequencing (2bRAD-M). Among them (21 subjects: 18 cholesterol and 3 pigment), plasma samples were subjected to liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics. The microbiome yielded 896 species comprising 882 bacteria, 13 fungi, and 1 archaeon. Microbial profiling revealed significant enrichment of Cutibacterium acnes and Microbacterium sp005774735 in gallstone and Agrobacterium pusense and Enterovirga sp013044135 in the bile of cholesterol GSD subjects. The metabolome revealed 2296 metabolites, in which malvidin 3-(6''-malonylglucoside), 2-Methylpropyl glucosinolate and ergothioneine were markedly enriched in cholesterol GSD subjects. Metabolite set enrichment analysis (MSEA) demonstrated enriched bile acids biosynthesis in individuals with cholesterol GSD. Overall, the multi-omics analysis revealed that microbiota and host metabolism interaction perturbations differ depending on the disease type. Perturbed gallstone type-related microbiota may contribute to unbalanced bile acids metabolism in the gallbladder and host, representing a potential early diagnostic marker and therapeutic target for GSD.</p>