Subclinical cholestasis is a hallmark of gut dysbiosis causing resistance to cancer immunotherapy
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE326943 | GEO | 2026/06/23
REPOSITORIES: GEO
Similar Datasets
Project description:Enterococcus faecalis is a natural inhabitant of the human gastrointestinal tract. In a healthy physiological state of the gut (eubiosis), E. faecalis is a subdominant species in the intestinal microbiota. When the intestinal homeostasis is disrupted (dysbiosis), it becomes dominant species and can cause infections. The prominence of bile acids deoxycholate (DCA) hallmarks eubiosis. This experiment aimed to better understand how E. faecalis adapts to DCA. We showed that DCA impairs E. faecalis growth and imposes permanent adjustments to the expression of many crucial genes, including a majority of factors enabling translation. Thus, the drastic decrease of DCA amounts during dysbiosis may account for the rise of E. faecalis population.
2022-05-20 | GSE192438 | GEO
Project description:The gut microbiome can impact brain health and is altered in Parkinson’s disease (PD) patients. The vermiform appendix is a lymphoid tissue implicated in the storage and regulation of the gut microbiome. Here, we investigate changes in the functional microbiome in the appendix of PD patients relative to controls by metatranscriptomic analysis. In the PD appendix, we find microbial dysbiosis affecting lipid metabolism, particularly an upregulation of bacteria responsible for secondary bile acid synthesis. Likewise, proteomic and transcript analysis in the PD gut corroborates a disruption in cholesterol homeostasis and lipid catabolism. Bile acid analysis in the PD appendix reveals an increase in the microbially-derived, toxic secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA). Synucleinopathy in mice induces similar microbiome alterations to those of PD patients and heightens microbial changes to gut inflammation. As observed in PD, the mouse model of synucleinopathy has elevated DCA and LCA. Raised levels of DCA and LCA can lead to liver injury, and an analysis of blood markers of liver dysfunction shows evidence of biliary abnormalities in PD patients, including elevated alkaline phosphatase and bilirubin. Increased bilirubin levels are also evident before PD diagnosis, in individuals at-risk of developing PD. In sum, microbially-derived toxic bile acids are heightened in PD and biliary changes may even precede the onset of overt motor symptoms.
2021-01-28 | PXD020988 | Pride
Project description:The gut microbiome can impact brain health and is altered in Parkinson’s disease (PD) patients. The vermiform appendix is a lymphoid tissue implicated in the storage and regulation of the gut microbiome. Here, we investigate changes in the functional microbiome in the appendix of PD patients relative to controls by metatranscriptomic analysis. In the PD appendix, we find microbial dysbiosis affecting lipid metabolism, particularly an upregulation of bacteria responsible for secondary bile acid synthesis. Likewise, proteomic and transcript analysis in the PD gut corroborates a disruption in cholesterol homeostasis and lipid catabolism. Bile acid analysis in the PD appendix reveals an increase in the microbially-derived, toxic secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA). Synucleinopathy in mice induces similar microbiome alterations to those of PD patients and heightens microbial changes to gut inflammation. As observed in PD, the mouse model of synucleinopathy has elevated DCA and LCA. Raised levels of DCA and LCA can lead to liver injury, and an analysis of blood markers of liver dysfunction shows evidence of biliary abnormalities in PD patients, including elevated alkaline phosphatase and bilirubin. Increased bilirubin levels are also evident before PD diagnosis, in individuals at-risk of developing PD. In sum, microbially-derived toxic bile acids are heightened in PD and biliary changes may even precede the onset of overt motor symptoms.
2021-08-01 | GSE156647 | GEO
Project description:Antibiotics (Abx) are critical in modern medicine but can induce intestinal dysbiosis, exacerbate inflammatory bowel diseases (IBD), and disrupt the gut microbiome. Moreover, Abx treatment was reported as a significant risk factor for developing IBD, yet the underlying mechanisms remain unknown. Here, we employed metagenomics and metaproteomics to investigate the impact of Abx treatment on gut microbiota composition and activity in non-IBD, pouchitis, and ulcerative colitis (UC) patients. The combined analysis revealed distinct microbiome profiles for each group and found that the metaproteomes are more susceptible to Abx-induced changes than metagenomes. Alpha diversity decreased across all cohorts during Abx treatment, with pouchitis and UC patients exhibiting dysbiosis before treatment. Taxonomic shifts, including blooms of Proteobacteria and Actinobacteria, and reductions in microbial pathway abundances were more pronounced in IBD patients. Proteomic analysis revealed an elevated abundance of host pancreatic proteases, particularly in non-IBD patients, and during Antibiotic treatment, correlating with increased proteolytic activity and impaired gut barrier function. Functional assays confirm differential fecal proteolytic activity, suggesting that bacterial protease inhibitors, which are significantly depleted during Abx treatment, regulate proteolysis and thereby maintain delicate homeostasis in the gut. Overall, our findings suggest that Abx treatment disrupts the balance between bacterial protease inhibitors and host proteases, contributing to inflammation and gut barrier disruption. This work underscores the importance of understanding Abx-induced proteolytic shifts in the context of IBD and highlights the utility of metaproteomics in elucidating host-microbiome interactions. Future research should investigate the molecular mechanisms underlying the abundance and activity of bacterial protease inhibitors, as well as their impact on gut health.
2026-04-29 | PXD066732 | Pride
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
Project description:Deoxycholic acid (DCA) is a secondary bile acid produced by a small number of commensal species of bacteria present in the mammalian gut. Elevated DCA concentration correlates with disease states including colon cancer and cholesterol gallstones, but the associated mechanisms are not fully understood. Both primary and secondary bile acids are also capable of affecting gene expression through nuclear receptors such as FXR. To better understand the impact of a commensal-derived secondary bile acid on host metabolism we fed DCA to germ-free (GF) mice, which normally lack DCA, and compared the hepatic transcriptomes of bile acid fed GF mice to GF mice receiving a control diet, as well as to those of conventionally housed control animals. Interestingly, the feeding of DCA to GF mice, but not the feeding of cholic acid (CA) from which DCA is derived, results in an up-regulation of genes of cholesterol biosynthetic pathways. GF mice normally have elevated hepatic cholesterol compared to conventionally housed mice. Despite increase in the expression of cholesterol biosynthetic genes, the DCA fed GF mice showed a markedly decreased level of hepatic cholesterol equivalent to the hepatic cholesterol concentration of conventionally colonized animals. Total cholesterol in the serum was unaffected by DCA, but there was a decrease in the HDL lipoprotein fraction as well as an increase in the non-HDL lipoprotein fraction of the serum cholesterol. DCA, but not CA, is sufficient to modulate host lipoprotein metabolism. Taken together, these results suggests that a minor component of the gut microbiome has a significant impact on cholesterol homeostasis through secondary metabolism of bile acids and suggests a possible therapeutic intervention route through the microbial metabolic pathways. two mouse strains, three diets, one time point
2015-01-08 | E-GEOD-34730 | biostudies-arrayexpress
Project description:Background: Although the bile acid-mediated microbiome-host interaction is known to shape both the composition and functionality of the gut microbiome, the mechanisms by which bile acid stress influences specific microbial metabolic interactions remain poorly understood. To address this gap, we examine the metabolic interplay between two key gut microbes. Bacteroides thetaiotaomicron, one of the most abundant species, possesses a broad enzymatic repertoire for polysaccharide degradation, while Collinsella aerofaciens is associated with liver-related diseases and plays a role in modifying primary bile acids. Results: In anaerobic coculture, C. aerofaciens mitigated the inhibitory effects of deoxycholic acid (DCA) on B. thetaiotaomicron by absorbing DCA from the medium and partially converting it into glycine-conjugated derivatives. Proteomic analysis showed that DCA broadly disrupted amino acid and vitamin metabolism pathways, particularly in B. thetaiotaomicron. In contrast, coculture led to a general upregulation of these pathways in C. aerofaciens, with a marked activation of vitamin B6 metabolism. Additionally, C. aerofaciens exhibited increased production of citrulline and ornithine in coculture. Conclusions: C. aerofaciens alleviates DCA toxicity on B. thetaiotaomicron through absorption, while promoting amino acid and vitamin metabolism, including the vitamin B6 synthesis pathway, during coculture. These results suggest that microbial interactions can enhance resistance to bile acid stress and may influence gut microbiome resilience, with potential relevance for liver- and bile acid–related disorders.
2026-01-06 | PXD069395 | Pride
Project description:Deoxycholic acid (DCA) is a secondary bile acid produced by a small number of commensal species of bacteria present in the mammalian gut. Elevated DCA concentration correlates with disease states including colon cancer and cholesterol gallstones, but the associated mechanisms are not fully understood. Both primary and secondary bile acids are also capable of affecting gene expression through nuclear receptors such as FXR. To better understand the impact of a commensal-derived secondary bile acid on host metabolism we fed DCA to germ-free (GF) mice, which normally lack DCA, and compared the hepatic transcriptomes of bile acid fed GF mice to GF mice receiving a control diet, as well as to those of conventionally housed control animals. Interestingly, the feeding of DCA to GF mice, but not the feeding of cholic acid (CA) from which DCA is derived, results in an up-regulation of genes of cholesterol biosynthetic pathways. GF mice normally have elevated hepatic cholesterol compared to conventionally housed mice. Despite increase in the expression of cholesterol biosynthetic genes, the DCA fed GF mice showed a markedly decreased level of hepatic cholesterol equivalent to the hepatic cholesterol concentration of conventionally colonized animals. Total cholesterol in the serum was unaffected by DCA, but there was a decrease in the HDL lipoprotein fraction as well as an increase in the non-HDL lipoprotein fraction of the serum cholesterol. DCA, but not CA, is sufficient to modulate host lipoprotein metabolism. Taken together, these results suggests that a minor component of the gut microbiome has a significant impact on cholesterol homeostasis through secondary metabolism of bile acids and suggests a possible therapeutic intervention route through the microbial metabolic pathways.
2015-01-08 | GSE34730 | GEO
Project description:Inflammatory bowel disease (IBD) relates to gut microbiota dysbiosis, bile acid (BA) disturbance and intestinal barrier impairment. We purified a fructose-dominant (Fru 93.63%) low-molecular-weight Polygonatum sibiricum polysaccharide (PSP). In 3% DSS-induced colitis in C57BL/6 mice, PSP (400 mg/kg/day) alleviated symptoms. Multi-omics showed PSP reversed DSS-induced disorders, regulated BA biosynthesis, restored barrier function and mitigated colitis, supporting its IBD intervention potential.
2026-01-26 | PXD073602 |