Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development

Mouriès, Juliette; Brescia, Paola; Silvestri, Alessandra; Spadoni, Ilaria; Sorribas, Marcel; Wiest, Reiner; Mileti, Erika; Galbiati, Marta; Invernizzi, Pietro; Adorini, Luciano; Penna, Giuseppe; Rescigno, María

doi:10.1016/j.jhep.2019.08.005

Cited by 465 publications

(410 citation statements)

References 49 publications

Supporting

Mentioning

397

Contrasting

Unclassified

Order By: Relevance

“…In patients with coeliac disease (CD) with elevated serum transaminases GVB alterations may be responsible for liver damage [59]. Although gut barrier disruption has not been reported to be a pre requisite for nonalcoholic steatohepatitis (NASH) development and belongs to the 'multiple hit' pathogenesis of disease progression [60], more recent observations in preclinical models have shown that disruption of epithelial and vascular barriers in the intestine were early events reported in NASH [61]. Gut-liver axis deterioration has also been described in patients with chronic liver diseases who develop sepsis and multiorgan failure [62,63].…”

Section: Discussionmentioning

confidence: 99%

COVID-19, MERS and SARS with Concomitant Liver Injury—Systematic Review of the Existing Literature

Kukla

Skonieczna-Żydecka

Kotfis

et al. 2020

JCM

103

View full text Add to dashboard Cite

The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but gastrointestinal symptoms and hepatic injury have also been reported. The mechanism of liver injury is poorly understood and may result as a consequence of viral hepatitis, systemic inflammatory response, gut barrier and microbiome alterations, intensive care treatment or drug toxicity. The incidence of hepatopathy among patients with coronavirus disease 2019 (COVID-19) is unclear, but studies have reported liver injury in patients with SARS and Middle East respiratory syndrome (MERS). We aimed to systematically review data on the prevalence of hepatic impairments and their clinical course in SARS and MERS Coronaviridae infections. A systematic literature search (PubMed/Embase/Cinahl/Web of Science) according to preferred reporting items for systematic review and meta-analysis protocols (PRISMA) was conducted from database inception until 17/03/2020 for studies that evaluated the incidence of hepatic abnormalities in SARS CoV-1, SARS CoV-2 and MERS infected patients with reported liver-related parameters. A total of forty-three studies were included. Liver anomalies were predominantly mild to moderately elevated transaminases, hypoalbuminemia and prolongation of prothrombin time. Histopathology varied between non-specific inflammation, mild steatosis, congestion and massive necrosis. More studies to elucidate the mechanism and importance of liver injury on the clinical course and prognosis in patients with novel SARS-CoV-2 infection are warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

COVID-19, MERS and SARS with Concomitant Liver Injury—Systematic Review of the Existing Literature

Kukla

Skonieczna-Żydecka

Kotfis

et al. 2020

JCM

103

View full text Add to dashboard Cite

show abstract

“…The integrity of this intestinal mucus barrier and the physiological composition of the intestinal microbiome are critical for maintaining homeostasis of the liver-gut axis [111]. Metabolic toxins, especially alcohol abuse or high fat/low fiber diet in NAFLD have been described to disrupt intestinal homeostasis by increasing intestinal permeability and altering microbiota [112,113]. Consequentially, the relative overgrowth of potentially pathogenic bacteria not only drives hepatic inflammatory immune responses and HSC activation due to portal delivery of pathogen-associated molecular patterns (PAMPs, as lipopolysaccharides, peptidoglycans, and flagellin), the altered microbiome also results in intestinal deconjugation of bile acids and therefore production of so-called secondary bile acids that suppress Farnesoid-X Receptor (FXR) signaling [111].…”

Section: Gut Dysbiosismentioning

confidence: 99%

“…FXR is a nuclear receptor activated by bile acids that regulates bile acid, lipid, and glucose metabolism [114,115]. Intestinal FXR signaling physiologically exert protective effects on intestinal epithelial barrier properties [116] and accelerates gut vascular barrier repair [113]. Intestinal accumulation of secondary FXR-suppressing bile acids in chronic liver disease therefore promotes disruption of the intestinal barrier.…”

Section: Gut Dysbiosismentioning

confidence: 99%

Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives

Roehlen

Crouchet

Baumert

2020

Cells

747

440

View full text Add to dashboard Cite

Liver fibrosis due to viral or metabolic chronic liver diseases is a major challenge of global health. Correlating with liver disease progression, fibrosis is a key factor for liver disease outcome and risk of hepatocellular carcinoma (HCC). Despite different mechanism of primary liver injury and disease-specific cell responses, the progression of fibrotic liver disease follows shared patterns across the main liver disease etiologies. Scientific discoveries within the last decade have transformed the understanding of the mechanisms of liver fibrosis. Removal or elimination of the causative agent such as control or cure of viral infection has shown that liver fibrosis is reversible. However, reversal often occurs too slowly or too infrequent to avoid life-threatening complications particularly in advanced fibrosis. Thus, there is a huge unmet medical need for anti-fibrotic therapies to prevent liver disease progression and HCC development. However, while many anti-fibrotic candidate agents have shown robust effects in experimental animal models, their anti-fibrotic effects in clinical trials have been limited or absent. Thus, no approved therapy exists for liver fibrosis. In this review we summarize cellular drivers and molecular mechanisms of fibrogenesis in chronic liver diseases and discuss their impact for the development of urgently needed anti-fibrotic therapies.

show abstract

“…The GVB, composed of endothelial cells, enteric glial cells and pericytes, prevents intestinal microbes from entering the body circulation [21,22]. Further, Mouries et al demonstrated that high-fat diet (HFD) induced dysbiosis that in turn disrupted GVB and drove the translocation of bacteria or their products into liver [23]. GVB-related research not only helps to understand the interaction between gut microbiota and intestinal barrier but also provides new insights into the prevention of NAFLD by regulation of gut-liver axis.…”

Section: Gut-liver Axismentioning

confidence: 99%

Intestinal microbiome and NAFLD: molecular insights and therapeutic perspectives

et al. 2019

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of dysregulated lipid and glucose metabolism, which is often associated with obesity, dyslipidemia and insulin resistance. In view of the high morbidity and health risks of NAFLD, the lack of effective cure has drawn great attention. In recent years, a line of evidence has suggested a close linkage between the intestine and liver diseases such as NAFLD. We summarized the composition and characteristics of intestinal microbes and reviewed molecular insights into the intestinal microbiome in development and progression of NAFLD. Intestinal microbes mainly include bacteria, archaea, viruses and fungi, and the crosstalk between non-bacterial intestinal microbes and human liver diseases should be paid more attention. Intestinal microbiota imbalance may not only increase the intestinal permeability to gut microbes but also lead to liver exposure to harmful substances that promote hepatic lipogenesis and fibrosis. Furthermore, we focused on reviewing the latest ''gut-liver axis''-targeting treatment, including the application of antibiotics, probiotics, prebiotics, synbiotics, farnesoid X receptor agonists, bile acid sequestrants, gut-derived hormones, adsorbents and fecal microbiota transplantation for NAFLD. In this review, we also discussed the potential mechanisms of ''gut-liver axis'' manipulation and efficacy of these therapeutic strategies for NAFLD treatment.

show abstract

Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development

Cited by 465 publications

References 49 publications

COVID-19, MERS and SARS with Concomitant Liver Injury—Systematic Review of the Existing Literature

COVID-19, MERS and SARS with Concomitant Liver Injury—Systematic Review of the Existing Literature

Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives

Intestinal microbiome and NAFLD: molecular insights and therapeutic perspectives

Contact Info

Product

Resources

About