Microbiota and Fatty Liver Disease—the Known, the Unknown, and the Future

Lang, Sonja; Schnabl, Bernd

doi:10.1016/j.chom.2020.07.007

Cited by 156 publications

(140 citation statements)

References 84 publications

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“…These observations underscore the importance of understanding how the gut microbiome evolves and contributes to NAFLD throughout disease progression. NAFLD-associated microbiota reportedly have reduced species alpha diversity [ 22 , 23 ]; however, changes to specific taxa have been inconsistent between studies [ 5 ]. Well-validated rodent models that faithfully recapitulate human NASH have been limited, but are critical tools to characterize the microbial changes associated with the progression to NASH and to establish any pathogenic role for the microbiota.…”

Section: Introductionmentioning

confidence: 99%

Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales

et al. 2021

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Background & aim Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) that is responsible for a growing fraction of cirrhosis and liver cancer cases worldwide. Changes in the gut microbiome have been implicated in NASH pathogenesis, but the lack of suitable murine models has been a barrier to progress. We have therefore characterized the microbiome in a well-validated murine NASH model to establish its value in modeling human disease. Methods The composition of intestinal microbiota was monitored in mice on a 12- or 24-week NASH protocol consisting of high fat, high sugar Western Diet (WD) plus once weekly i.p injection of low-dose CCl4. Additional mice were subjected to WD-only or CCl4-only conditions to assess the independent effect of these variables on the microbiome. Results There was substantial remodeling of the intestinal microbiome in NASH mice, characterized by declines in both species diversity and bacterial abundance. Based on changes to beta diversity, microbiota from NASH mice clustered separately from controls in principal coordinate analyses. A comparison between WD-only and CCl4-only controls with the NASH model identified WD as the primary driver of early changes to the microbiome, resulting in loss of diversity within the 1st week. A NASH signature emerged progressively at weeks 6 and 12, including, most notably, a reproducible bloom of the Firmicute order Erysipelotrichales. Conclusions We have established a valuable model to study the role of gut microbes in NASH, enabling us to identify a new NASH gut microbiome signature.

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Section: Introductionmentioning

confidence: 99%

Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales

et al. 2021

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“…The major changes in gut permeability and microbiota composition, form an additional plausible harmful “hit”. Multiple alterations can be observed that range from reduced microbial diversity, abundance of pathogenic microbiota, accumulation of bacterial metabolites, changes to the intestinal virome and reduced intestinal barrier ( 33 , 34 ). With these changes, an increased release of pathogen-associated molecular patterns (PAMPs), e.g., lipopolysaccharide (LPS) can be observed in the portal vein and the systemic circulation, which stimulate the respective PRRs expressed by the various liver cells, and therefore further contribute to the pro-inflammatory liver environment ( 35 ).…”

Section: Inflammatory Processes During Nashmentioning

confidence: 99%

Controversies and Opportunities in the Use of Inflammatory Markers for Diagnosis or Risk Prediction in Fatty Liver Disease

Lambrecht

Tacke

2021

Front. Immunol.

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In the Western society, non-alcoholic fatty liver disease (NAFLD), characterized by the excessive accumulation of fat in the liver, represents the most common cause of chronic liver disease. If left untreated, approximately 15%–20% of patients with NAFLD will progress to non-alcoholic steatohepatitis (NASH), in which lobular inflammation, hepatocyte ballooning and fibrogenesis further contribute to a distorted liver architecture and function. NASH initiation has significant effects on liver-related mortality, as even the presence of early stage fibrosis increases the chances of adverse patient outcome. Therefore, adequate diagnostic tools for NASH are needed, to ensure that relevant therapeutic actions can be taken as soon as necessary. To date, the diagnostic gold standard remains the invasive liver biopsy, which is associated with several drawbacks such as high financial costs, procedural risks, and inter/intra-observer variability in histology analysis. As liver inflammation is a major hallmark of disease progression, inflammation-related circulating markers may represent an interesting source of non-invasive biomarkers for NAFLD/NASH. Examples for such markers include cytokines, chemokines or shed receptors from immune cells, circulating exosomes related to inflammation, and changing proportions of peripheral blood mononuclear cell (PBMC) subtypes. This review aims at documenting and critically discussing the utility of such novel inflammatory markers for NAFLD/NASH-diagnosis, patient stratification and risk prediction.

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“…The primary methods by which the intestine communicates with the liver is through the hepatic portal vein, hepatic biliary system, and by using other potential intermediary substances for maintaining normal physiological conditions [ 8 ]. As a natural inhabitant of the intestine, gut microbiota serves as invaluable contributors to gut health as well as in the pathophysiology of numerous diseases [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota at the Intersection of Alcohol, Brain, and the Liver

Gupta

Suk

Kim

2021

JCM

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Over the last decade, increased research into the cognizance of the gut–liver–brain axis in medicine has yielded powerful evidence suggesting a strong association between alcoholic liver diseases (ALD) and the brain, including hepatic encephalopathy or other similar brain disorders. In the gut–brain axis, chronic, alcohol-drinking-induced, low-grade systemic inflammation is suggested to be the main pathophysiology of cognitive dysfunctions in patients with ALD. However, the role of gut microbiota and its metabolites have remained unclear. Eubiosis of the gut microbiome is crucial as dysbiosis between autochthonous bacteria and pathobionts leads to intestinal insult, liver injury, and neuroinflammation. Restoring dysbiosis using modulating factors such as alcohol abstinence, promoting commensal bacterial abundance, maintaining short-chain fatty acids in the gut, or vagus nerve stimulation could be beneficial in alleviating disease progression. In this review, we summarize the pathogenic mechanisms linked with the gut–liver–brain axis in the development and progression of brain disorders associated with ALD in both experimental models and humans. Further, we discuss the therapeutic potential and future research directions as they relate to the gut–liver–brain axis.

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Microbiota and Fatty Liver Disease—the Known, the Unknown, and the Future

Cited by 156 publications

References 84 publications

Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales

Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales

Controversies and Opportunities in the Use of Inflammatory Markers for Diagnosis or Risk Prediction in Fatty Liver Disease

Gut Microbiota at the Intersection of Alcohol, Brain, and the Liver

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