Intestinal Virome Signature Associated With Severity of Nonalcoholic Fatty Liver Disease

Lang, Sonja; Demir, Münevver; Martin, Anna; Jiang, Lu; Zhang, Xinlian; Duan, Yi; Gao, Bei; Wisplinghoff, Hilmar; Kasper, Philipp; Roderburg, Christoph; Tacke, Frank; Steffen, Hans‐Michael; Goeser, Tobias; Abraldes, Juan G.; Tu, Xin; Loomba, Rohit; Stärkel, Peter; Pride, David T.; Fouts, Derrick E.; Schnabl, Bernd

doi:10.1053/j.gastro.2020.07.005

Cited by 127 publications

(115 citation statements)

References 47 publications

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“…Presence of phages often (though not always) correlate positively with their respective hosts [29]. In contrast, the virome in patients with non-alcoholic fatty liver disease does not show an enrichment in eukaryotic viruses, therefore this seems to be specific for AH [30]. Table 1 summarizes the most common changes of the bacterial microbiota, mycobiome and virome in patients with ALD.…”

Section: Intestinal Virome Changes In Patients With Alcohol Related Lmentioning

confidence: 99%

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Gut dysbiosis as a driver in alcohol-induced liver injury

Fairfield

Schnabl

2021

JHEP Reports

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Summary Alcohol-related liver disease characterises a broad spectrum of hepatic diseases that result from heavy alcohol use, and include alcohol-related steatosis, steatohepatitis, fibrosis, cirrhosis, and alcoholic hepatitis. Amongst heavy drinkers, progression to more severe forms of alcohol-related liver disease is not universal, with only 20% developing cirrhosis and up to one-third developing alcoholic hepatitis. Non-alcohol-related triggers for severe disease are not well understood, but the intestinal microbiome is thought to be a contributing factor. This review examines the role of the microbiome in mild alcohol-related liver disease, cirrhosis, and alcoholic hepatitis. While most of the literature discusses bacterial dysbiosis, we also discuss the available evidence on fungal (mycobiome) and virome alterations in patients with alcohol-related liver disease. Additionally, we explore the mechanisms by which the microbiome contributes to the pathogenesis of alcohol-related liver disease, including effects on intestinal permeability, bile acid dysregulation, and production of hepatotoxic virulence factors.

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Section: Intestinal Virome Changes In Patients With Alcohol Related Lmentioning

confidence: 99%

“… 29 In contrast, the virome in patients with non-alcoholic fatty liver disease does not show an enrichment in eukaryotic viruses, therefore this seems to be specific for AH. 30 …”

Section: Intestinal Virome Changes In Patients With Alcohol-related Lmentioning

confidence: 99%

Gut dysbiosis as a driver in alcohol-induced liver injury

Fairfield

Schnabl

2021

JHEP Reports

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“…The virome has only been investigated in NAFLD, alcoholic hepatitis, and cirrhotic patients [300][301][302]. In NAFLD, 420 different viral species were detected in all patients, but only 19 of them were found in at least 50% of all fecal samples.…”

Section: Liver Diseasesmentioning

confidence: 99%

The Gut-Liver Axis in Cholestatic Liver Diseases

Blesl

Stadlbauer

2021

Nutrients

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The gut-liver axis describes the physiological interplay between the gut and the liver and has important implications for the maintenance of health. Disruptions of this equilibrium are an important factor in the evolution and progression of many liver diseases. The composition of the gut microbiome, the gut barrier, bacterial translocation, and bile acid metabolism are the key features of this cycle. Chronic cholestatic liver diseases include primary sclerosing cholangitis, the generic term secondary sclerosing cholangitis implying the disease secondary sclerosing cholangitis in critically ill patients and primary biliary cirrhosis. Pathophysiology of these diseases is not fully understood but seems to be multifactorial. Knowledge about the alterations of the gut-liver axis influencing the pathogenesis and the outcome of these diseases has considerably increased. Therefore, this review aims to describe the function of the healthy gut-liver axis and to sum up the pathological changes in these cholestatic liver diseases. The review compromises the actual level of knowledge about the gut microbiome (including the mycobiome and the virome), the gut barrier and the consequences of increased gut permeability, the effects of bacterial translocation, and the influence of bile acid composition and pool size in chronic cholestatic liver diseases. Furthermore, therapeutic implications and future scientific objectives are outlined.

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“…As evident from comparing inbred laboratory mouse strains to true "wild type" mice in natural forests, the composition of the gut microbiota shapes the responsiveness of hepatic immune cells, thereby contributing to the host's immune fitness and resilience against diseases [165,166]. More recently, other components of the gut microbiome such as viroids and fungi were found to be dysregulated in NAFLD as well [167].…”

Section: Gut-liver Axismentioning

confidence: 99%

Inflammatory Mechanisms Underlying Nonalcoholic Steatohepatitis and the Transition to Hepatocellular Carcinoma

Peiseler

Tacke

2021

Cancers

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Nonalcoholic fatty liver disease (NAFLD) is a rising chronic liver disease and comprises a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) to end-stage cirrhosis and risk of hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is multifactorial, but inflammation is considered the key element of disease progression. The liver harbors an abundance of resident immune cells, that in concert with recruited immune cells, orchestrate steatohepatitis. While inflammatory processes drive fibrosis and disease progression in NASH, fueling the ground for HCC development, immunity also exerts antitumor activities. Furthermore, immunotherapy is a promising new treatment of HCC, warranting a more detailed understanding of inflammatory mechanisms underlying the progression of NASH and transition to HCC. Novel methodologies such as single-cell sequencing, genetic fate mapping, and intravital microscopy have unraveled complex mechanisms behind immune-mediated liver injury. In this review, we highlight some of the emerging paradigms, including macrophage heterogeneity, contributions of nonclassical immune cells, the role of the adaptive immune system, interorgan crosstalk with adipose tissue and gut microbiota. Furthermore, we summarize recent advances in preclinical and clinical studies aimed at modulating the inflammatory cascade and discuss how these novel therapeutic avenues may help in preventing or combating NAFLD-associated HCC.

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Intestinal Virome Signature Associated With Severity of Nonalcoholic Fatty Liver Disease

Cited by 127 publications

References 47 publications

Gut dysbiosis as a driver in alcohol-induced liver injury

Gut dysbiosis as a driver in alcohol-induced liver injury

The Gut-Liver Axis in Cholestatic Liver Diseases

Inflammatory Mechanisms Underlying Nonalcoholic Steatohepatitis and the Transition to Hepatocellular Carcinoma

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