The Gut-Liver Axis in Cholestatic Liver Diseases

Blesl, Andreas; Stadlbauer, Vanessa

doi:10.3390/nu13031018

Cited by 43 publications

(30 citation statements)

References 349 publications

(433 reference statements)

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“…In addition, considering that the correlation with SCFAs was stronger for T-Bil than for ALT, cholestasis might be the main contributor to the pathogenesis of these phenomena rather than the hepatocellular damage itself. Although bile acids are known to play an essential role in regulating the intestinal immune system ( 32 , 33 , 34 ), our findings confirmed that SCFAs depletion is a key mechanism connecting dysbiosis caused by reduced amounts of bile acids within the intestine and intestinal barrier dysfunction in liver disease.…”

Section: Discussionsupporting

confidence: 74%

Dysbiosis and Depletion of Fecal Organic Acids Correlate With the Severity of Rejection After Rat Liver Transplantation

Yao¹,

Yagi²,

Ogawa³

et al. 2022

Transpl Int

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The impact of T cell-mediated rejection (TCMR) after liver transplantation (LT) on the alterations in the gut microbiota (GM) and associated intestinal environment represented by fecal organic acids (OAs) require further elucidation. A rat allogeneic LT model was prepared without immunosuppressants or antibiotics, and a syngeneic model was used as a control. Qualitative and quantitative analyses of fecal samples at fixed time points were performed. Correlation analyses were also performed between liver function and GMs and OA levels. In the allogeneic TCMR group, the number of predominant obligate anaerobes decreased as liver function declined. Clostridioides difficile, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus were significantly increased. Regarding fecal OA concentration, short-chain fatty acid (SCFA) concentrations were depleted as liver function declined. In contrast, in the syngeneic group, GM and OAs exhibited only slight, transient, and reversible disturbances. In addition, alanine aminotransferase and total bilirubin were positively correlated with the number of Enterobacteriaceae and Enterococcus, and negatively correlated with the fecal concentration of SCFAs. The allogeneic TCMR model demonstrated distinct dysbiosis and depletion of fecal OAs as TCMR progressed after LT. The degree of graft injury was closely related to the number of specific bacterial strains and the concentrations of fecal SCFAs.

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Section: Discussionsupporting

confidence: 74%

Dysbiosis and Depletion of Fecal Organic Acids Correlate With the Severity of Rejection After Rat Liver Transplantation

Yao¹,

Yagi²,

Ogawa³

et al. 2022

Transpl Int

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“…In turn, bile acids also alter gut microbiome, resulting in an inextricable codependent relationship which forms an important element of the gut–liver axis. [ 65 ]…”

Section: Microbesmentioning

confidence: 99%

Mechanisms and molecules: What are the treatment targets for primary biliary cholangitis?

Mayo

2022

Hepatology

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Treatment of primary biliary cholangitis (PBC) with ursodeoxycholic acid (UDCA) is not always sufficient to prevent progression to hepatic decompensation and/or need for liver transplant. Adjuvant therapy with obeticholic acid may provide additional biochemical improvements in some patients, but it is not well-tolerated by patients with significant itch or advanced cirrhosis. Thus, new and creative approaches to treating patients with PBC are important to identify. This review discusses major potential therapeutic targets in PBC and provides examples of some specific agents currently in development for the treatment of PBC. Targets are broadly classified into those which strive to modify bile, inflammation, cell survival, or fibrosis. In bile, shrinking the size of the bile acid pool or modifying the quality of the bile by making it more hydrophilic or enriched in phosphatidylcholine may ameliorate cholestatic injury.Biliary epithelial cell survival may be extended by fortifying the bicarbonate umbrella or improving cell membrane integrity. Autoimmunity and cholangitis have the potential to be improved via regulation of the immune system.Targeting cytokines, immune checkpoints, and anti-mitochondrial antibodies are examples of a more focused immunosuppression approach. Stem cell therapy and lymphocyte trafficking inhibition are more novel methods of broad immune regulation. Anti-fibrotic therapies are also potentially useful for preventing progression of PBC. The nuclear hormone receptors, farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) regulate many of these pathways: cholestasis, inflammation, and fibrosis, which is why they are being enthusiastically pursued as potential therapeutic targets in PBC.

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“…In the presented case, a string-positive E. coli strain was isolated from a patient with recurrent bacteremia, conjecturally causative colligated with the patient’s cholestatic cholangitis. The occurrence of E. coli in the biliary tract is well known, for example as a cause of gallstones [ 19 , 20 ]. Intestinal bacteria such as E. coli , especially ExPEC, are able to invade the biliary tract during bile stasis, resulting in an acute infection [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Recurrent bacteremia with a hypermucoviscous Escherichia coli isolated from a patient with perihilar cholangiocarcinoma: insights from a comprehensive genome-based analysis

Neumann

Lippmann

Wendt

et al. 2022

Ann Clin Microbiol Antimicrob

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Background Escherichia coli (E. coli) is a common human pathogen, responsible for a broad spectrum of infections. Sites of infection can vary, but the hepato-biliary system is of particular concern due to the infection-associated formation of gallstones and the spread of pathogens from the bile ducts into the bloodstream. Case presentation The presented case is striking, as the detected isolate showed a positive string test. This hypermucoviscous phenotype is atypical for E. coli and a particular feature of hypervirulent Klebsiella pneumoniae (K. pneumoniae) variants. Objectives To provide new insights into the genomic background of an E. coli strain with an unusual hypermucoviscous phenotype using hybrid short- and long-read sequencing approaches. Results Complete hybrid assemblies of the E. coli genome and plasmids were done and used for genome based typing. Isolate 537–20 was assigned to the multilocus sequence type ST88 and serotype O8:H4. The strain showed a close relationship to avian pathogenic strains. Analysis of the chromosome and plasmids revealed the presence of several virulence factors, such as the Conserved Virulence Plasmidic (CVP) region on plasmid 537-20_1, including several iron acquisition genes (sitABCD, iroABCDEN, iucABCD, hbd) and the iutA gene encoding the receptor of the siderophore aerobactin. The hypermucoviscous phenotype could be caused by encapsulation of putative K. pneumoniae origin. Conclusions Hybrid sequencing enabled detailed genomic characterization of the hypermucoviscous E. coli strain, revealing virulence factors that have their putative origin in K. pneumoniae.

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The Gut-Liver Axis in Cholestatic Liver Diseases

Cited by 43 publications

References 349 publications

Dysbiosis and Depletion of Fecal Organic Acids Correlate With the Severity of Rejection After Rat Liver Transplantation

Dysbiosis and Depletion of Fecal Organic Acids Correlate With the Severity of Rejection After Rat Liver Transplantation

Mechanisms and molecules: What are the treatment targets for primary biliary cholangitis?

Recurrent bacteremia with a hypermucoviscous Escherichia coli isolated from a patient with perihilar cholangiocarcinoma: insights from a comprehensive genome-based analysis

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