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.

2021-07-08 | GSE179524 | GEO

Gut microbiota and gallstone formation - cohousing study

Project description:Gut microbiota and gallstone formation - cohousing study

| PRJEB35631 | ENA

Opioid-induced gut microbial disruption leads to gut barrier compromise and sustained systemic inflammation.

Project description:Morphine and its pharmacological derivatives are the most prescribed analgesics for moderate to severe pain management. However, chronic use of morphine reduces pathogen clearance and induces bacterial translocation across the gut barrier. The enteric microbiome has been shown to play a critical role in the preservation of the mucosal barrier function and metabolic homeostasis. Here, we show for the first time, using bacterial 16s rDNA sequencing, that chronic morphine treatment significantly alters the gut microbial composition and induces preferential expansion of the gram-positive pathogenic and reduction of bile-deconjugating bacterial strains. A significant reduction in both primary and secondary bile acid levels was seen in the gut, but not in the liver with morphine treatment. Morphine induced microbial dysbiosis and gut barrier disruption was rescued by transplanting placebo-treated microbiota into morphine-treated animals, indicating that microbiome modulation could be exploited as a therapeutic strategy for patients using morphine for pain management. In this study, we establish a link between the two phenomena, namely gut barrier compromise and dysregulated bile acid metabolism. We show for the first time that morphine fosters significant gut microbial dysbiosis and disrupts cholesterol/bile acid metabolism. Changes in the gut microbial composition is strongly correlated to disruption in host inflammatory homeostasis13,14 and in many diseases (e.g. cancer/HIV infection), persistent inflammation is known to aid and promote the progression of the primary morbidity. We show here that chronic morphine, gut microbial dysbiosis, disruption of cholesterol/bile acid metabolism and gut inflammation; have a linear correlation. This opens up the prospect of devising minimally invasive adjunct treatment strategies involving microbiome and bile acid modulation and thus bringing down morphine-mediated inflammation in the host.

2016-06-01 | E-MTAB-3722 | biostudies-arrayexpress

Germfree C57BL/6J mice are resistant to high fat diet-induced insulin resistance and have altered cholesterol metabolism

Project description:Germfree (GF) mice have been used as a model to study the contribution of the intestinal microbiota to metabolic energy balance of the host. Despite a wealth of knowledge accumulated since the 1940’s, the response of GF mice to a high fat diet is largely unknown. In the present study, we compared the metabolic consequences of a high fat (HF) diet on GF and conventional (Conv) C57BL/6J mice. As expected, Conv mice developed obesity and glucose intolerance with a HF diet. In contrast, GF mice remained lean and resisted the HF diet-induced insulin resistance. The anti-obesity phenotype of GF/HF mice was accompanied by reduced caloric intake, diminished food efficiency, and excessive fecal lipid excretion contributed to the reduced food efficiency. In addition, HF diet-induced hypercholesterolemia was ameliorated, which was partially due to an increase in fecal cholesterol excretion. However, hepatic cholesterols were increased in GF/HF mice. Elevated nuclear SREBP2 proteins and the up-regulation of cholesterol biosynthesis genes support the increased liver cholesterol biosynthesis in GF/HF mice. The resistance to HF diet-induced metabolic abnormalities in GF mice was also associated with a reduced immune response, indicated by low plasma pro-inflammatory and anti-inflammatory markers. These data suggest that the gut microbiota of Conv mice contributes to HF diet-induced obesity, insulin resistance, dyslipidemia and hepatic steatosis in mice. Thus, results of the present study describe the metabolic responses of GF mice to a HF diet and further our understandings of the relationship between the gut microbiota and the host. Germfree and conventional C57BL/6J mice were fed with a high fat diet for 11 weeks. Then, all mice were sacrified under 10-h food deprevation, and liver samples of germfree (n=14) and conventional (n=16) were examined.

2010-08-20 | E-GEOD-19038 | biostudies-arrayexpress

Bile-induced biofilm formation in Bacteroides thetaiotaomicron requires magnesium efflux by an RND pump

Project description:The study is about the role of Bacteroides thetaiotaomicron in the human gut microbiota, specifically its ability to form biofilms in response to bile salts. The study found that bile induces the expression of certain efflux pumps, and inhibiting these pumps impairs biofilm formation. Among the induced pumps, the BipABC pump is crucial for biofilm formation as it is involved in the efflux of magnesium, which affects the biofilm's extracellular matrix and structure. This discovery sheds light on how intestinal chemical cues, like bile salts, regulate biofilm formation in B. thetaiotaomicron, a significant gut symbiont.

2024-03-19 | E-MTAB-13460 | biostudies-arrayexpress

Chaihu Shugan prevents cholesterol gallstone formation by ameliorating the microbiota dysbiosis and metabolic disturbance in mice

Project description:INTRODUCTION: 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.METHODS: We examined the in vivo 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.RESULTS: The intestinal microbiota was severely dysregulated during the formation of CGS, showing a marked decrease in the abundance of beneficial microbiota, especially Lactobacillus and Akkermansia. 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.CONCLUSION: Our data show that Chaihu Shugan can prevent CGS and indicate its mechanisms of action.

2024-01-29 | MTBLS7181 | MetaboLights

Project description:GUT MICROBIOTA AND GALLSTONE - gallstone free

| PRJNA589944 | ENA