Bile Duct Colonization With Enterococcus sp. Associates With Disease Progression in Primary Sclerosing Cholangitis

Zigmond, Ehud; Zecher, Britta Franziska; Bartels, A.; Ziv‐Baran, Tomer; Rösch, Thomas; Schachschal, Guido; Lohse, Ansgar W.; Ehlken, Hanno; Schramm, Christoph

doi:10.1016/j.cgh.2022.09.006

Cited by 24 publications

(14 citation statements)

References 27 publications

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“…Clinically, bile duct colonization with Enterococcus spp . correlated with disease progression in PSC, highlighting the potential importance of bacteria in this disease 232 . In liver cirrhosis, fecal concentrations of Proteobacteria and Fusobacteria are highly increased 233 .…”

Section: Microbiomementioning

confidence: 96%

“…correlated with disease progression in PSC, highlighting the potential importance of bacteria in this disease. [232] In liver cirrhosis, fecal concentrations of Proteobacteria and Fusobacteria are highly increased. [233] Prevalence of potentially pathogenic bacteria, such as Enterobacteriaceae and Streptococcaceae, affected clinical phenotype and prognosis in these patients and changes in the gut microbiome accompanied cirrhosis decompensation.…”

Section: The Microbiome As a Driver Of Liver Diseasementioning

confidence: 99%

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Therapeutic modulation of the liver immune microenvironment

2023

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Inflammation is a hallmark of progressive liver diseases such as chronic viral or immune-mediated hepatitis, alcohol-associated liver disease, and NAFLD. Preclinical and clinical studies have provided robust evidence that cytokines and related cellular stress sensors in innate and adaptive immunity orchestrate hepatic disease processes. Unresolved inflammation and liver injury result in hepatic scarring, fibrosis, and cirrhosis, which may culminate in HCC. Liver diseases are accompanied by gut dysbiosis and a bloom of pathobionts, fueling hepatic inflammation. Anti-inflammatory strategies are extensively used to treat human immune-mediated conditions beyond the liver, while evidence for immunomodulatory therapies and cell therapy–based strategies in liver diseases is only emerging. The development and establishment of novel immunomodulatory therapies for chronic liver diseases has been dampened by several clinical challenges, such as invasive monitoring of therapeutic efficacy with liver biopsy in clinical trials and risk of DILI in several studies. Such aspects prevented advancements of novel medical therapies for chronic inflammatory liver diseases. New concepts modulating the liver immune environment are studied and eagerly awaited to improve the management of chronic liver diseases in the future.

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Section: Microbiomementioning

confidence: 96%

Section: The Microbiome As a Driver Of Liver Diseasementioning

confidence: 99%

Therapeutic modulation of the liver immune microenvironment

2023

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“…As far as the biliary microbiome is concerned, Zigmond E et al demonstrated, in a cohort of 189 patients affected by PSC undergoing endoscopic retrograde cholangiopancreatography (ERCP) for bile fluid collection, the presence of Enterococci that conferred risk of disease progression, such as fungobilia [ 58 ]. Additionally, Liwinsky et al observed that the bile fluid of PSC patients was enriched by the presence of Enterococcus faecalis , a potentially pathogenic bacterium ( Table 2 ) involved in an increase of the bile acid, taurolithocholic acid, which is known to be pro-inflammatory and potentially carcinogenic [ 60 ].…”

Section: Pscmentioning

confidence: 99%

Role of the Gut–Liver Axis in the Pathobiology of Cholangiopathies: Basic and Clinical Evidence

Bragazzi

Venere

Vignone

et al. 2023

IJMS

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The “Gut–Liver Axis” refers to the physiological bidirectional interplay between the gut and its microbiota and the liver which, in health, occurs thanks to a condition of immune tolerance. In recent years, several studies have shown that, in case of a change in gut bacterial homeostasis or impairment of intestinal barrier functions, cholangiocytes, which are the epithelial cells lining the bile ducts, activate innate immune responses against gut-derived microorganisms or bacterial products that reach the liver via enterohepatic circulation. Intestinal dysbiosis or impaired intestinal barrier functions cause cholangiocytes to be exposed to an increasing amount of microorganisms that can reactivate inflammatory responses, thus inducing the onset of liver fibrosis. The present review focuses on the role of the gut–liver axis in the pathogenesis of cholangiopathies.

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“…Free fatty acids and endotoxins may flow into the portal circulation and hepatic sinusoids as a result of dysfunction of the intestinal epithelial barrier, which may then result in liver damage and inflammation ( 122 , 123 ). Endotoxins have been shown to enhance the sensitivity of hepatocytes to cell death in response to bile acid challenge ( 124 ).…”

Section: Inflammasomes and Pyroptosis In Aildsmentioning

confidence: 99%

Inflammasome and pyroptosis in autoimmune liver diseases

et al. 2023

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Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and IgG4-related sclerosing cholangitis (IgG4-SC) are the four main forms of autoimmune liver diseases (AILDs), which are all defined by an aberrant immune system attack on the liver. Most previous studies have shown that apoptosis and necrosis are the two major modes of hepatocyte death in AILDs. Recent studies have reported that inflammasome-mediated pyroptosis is critical for the inflammatory response and severity of liver injury in AILDs. This review summarizes our present understanding of inflammasome activation and function, as well as the connections among inflammasomes, pyroptosis, and AILDs, thus highlighting the shared features across the four disease models and gaps in our knowledge. In addition, we summarize the correlation among NLRP3 inflammasome activation in the liver-gut axis, liver injury, and intestinal barrier disruption in PBC and PSC. We summarize the differences in microbial and metabolic characteristics between PSC and IgG4-SC, and highlight the uniqueness of IgG4-SC. We explore the different roles of NLRP3 in acute and chronic cholestatic liver injury, as well as the complex and controversial crosstalk between various types of cell death in AILDs. We also discuss the most up-to-date developments in inflammasome- and pyroptosis-targeted medicines for autoimmune liver disorders.

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Bile Duct Colonization With Enterococcus sp. Associates With Disease Progression in Primary Sclerosing Cholangitis

Cited by 24 publications

References 27 publications

Therapeutic modulation of the liver immune microenvironment

Therapeutic modulation of the liver immune microenvironment

Role of the Gut–Liver Axis in the Pathobiology of Cholangiopathies: Basic and Clinical Evidence

Inflammasome and pyroptosis in autoimmune liver diseases

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