Intestinal and hepatic microbiota changes associated with chronic ethanol administration in mice

Bluemel, Sena; Wang, Lirui; Kuelbs, Claire; Moncera, Kelvin; Torralba, Manolito; Singh, Harinder; Fouts, Derrick E.; Schnabl, Bernd

doi:10.1080/19490976.2019.1595300

Cited by 39 publications

(30 citation statements)

References 48 publications

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“…76 Alcohol consumption can increase intestinal bacterial and fungal dysbiosis, which contribute to disease susceptibility, loss of gut barrier function, and progression of liver injury. [77][78][79][80] Mice given antibiotics develop less severe liver injury, and do not have intestinal reductions in occludin expression, with ethanol feeding. 74,81 However, germ-free mice, which lack commensal bacteria, develop more severe ethanol-induced injury than conventionally housed mice (with commensal bacteria).…”

Section: Alcohol-induced Liver Diseasementioning

confidence: 99%

Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders

2020

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Intestinal barrier dysfunction and dysbiosis contribute to development of diseases in liver and other organs. Physical, immunologic, and microbiologic (bacterial, fungal, archaeal, viral, and protozoal) features of the intestine separate its nearly 100 trillion microbes from the rest of the human body. Failure of any aspect of this barrier can result in translocation of microbes into the blood and sustained inflammatory response that promote liver injury, fibrosis, cirrhosis, and oncogenic transformation. Alterations in intestinal microbial populations or their functions can also affect health. We review the mechanisms that regulate intestinal permeability and how changes in the intestinal microbiome contribute to development of acute and chronic liver diseases. We discuss individual components of the intestinal barrier and how these are disrupted during development of different liver diseases. Learning more about these processes will increase our understanding of the interactions among the liver, intestine, and its flora.

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Section: Alcohol-induced Liver Diseasementioning

confidence: 99%

Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders

2020

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“…Increased intestinal permeability is a common feature in preclinical models of ethanol-induced liver disease. 101 In addition, microbial derived products appear to play an important role for ethanol-induced liver disease in mice. Mice with genetic deletions in the LPS signaling pathway are resistant to alcohol-induced liver damage.…”

Section: Bacterial Translocationmentioning

confidence: 99%

“…Moreover, gram-negative Prevotella not only increased in the mucus layer of the ileum but also in liver samples suggesting that translocation of viable bacteria to the liver might be associated with microbiota changes in the distal gastrointestinal tract. 101 Gastric acid suppression by proton pump inhibitor increases intestinal Enterococcus and its translocation to the liver, exacerbating ethanol-induced liver disease both in mice and humans. 103 E. faecalis was detectable in the liver of mice given cytolytic and non-cytolytic E. faecalis and fed an ethanol diet, but not when mice were fed a control diet indicating that ethanol-induced changes in the gut barrier are necessary for the translocation of cytolytic E. faecalis.…”

Section: Bacterial Translocationmentioning

confidence: 99%

From intestinal dysbiosis to alcohol-associated liver disease

Mendes

Schnabl

2020

Clin Mol Hepatol

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Alcohol-associated intestinal dysbiosis and bacterial overgrowth can lead to a dysregulation of tryptophan metabolism and lower production of indoles. Several of these indole derivatives are aryl hydrocarbon receptor ligands that, in turn, are involved in antimicrobial defense via induction of interleukin-22 (IL-22). IL-22 increases the expression of intestinal regenerating islet-derived 3 (Reg3) lectins, which maintain low bacterial colonization of the inner mucus layer and reduce bacterial translocation to the liver. Chronic alcohol consumption is associated with reduced intestinal expression of Reg3β and Reg3γ, increased numbers of mucosa-associated bacteria and bacterial translocation. Translocated microbial products and viable bacteria reach the liver and activate the innate immune system. Release of inflammatory molecules promotes inflammation, contributes to hepatocyte death and results in a fibrotic response. This review summarizes the mechanisms by which chronic alcohol intake changes the gut microbiota and contributes to alcohol-associated liver disease by changing microbial-derived metabolites.

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“…In patients with AH compared to non-alcohol consuming controls, there was an increase in isoprenoid synthesis through upregulation of the mevalonate and anthranilate degradation, which are known modulators of gram-positive bacterial growth and biofilm production, respectively. Bluemel et al 53 investigated the microbiota in the jejunum, ileum, cecum, feces and liver of mice subjected to chronic ethanol feeding; they found that chronic ethanol administration modified alpha diversity in the ileum and the liver, largely driven by an increase in gram-negative phyla, resulting in endotoxemia. Specifically, the gram-negative Prevotella increased in the mucus layer of the ileum and also in liver tissues, suggesting the central role of dysbiosis and bacterial translocation leading to liver injury with alcohol use.…”

Section: Aldmentioning

confidence: 99%

Modulating the Intestinal Microbiota: Therapeutic Opportunities in Liver Disease

Philips¹,

Augustine²,

Yerol³

et al. 2019

Journal of Clinical and Translational Hepatology

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Gut microbiota has been demonstrated to have a significant impact on the initiation, progression and development of complications associated with multiple liver diseases. Notably, nonalcoholic fatty liver diseases, including nonalcoholic steatohepatitis and cirrhosis, severe alcoholic hepatitis, primary sclerosing cholangitis and hepatic encephalopathy, have strong links to dysbiosisor a pathobiological change in the microbiota. In this review, we provide clear and concise discussions on the human gut microbiota, methods of identifying gut microbiota and its functionality, liver diseases that are affected by the gut microbiota, including novel associations under research, and provide current evidence on the modulation of gut microbiota and its effects on specific liver disease conditions.

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Intestinal and hepatic microbiota changes associated with chronic ethanol administration in mice

Cited by 39 publications

References 48 publications

Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders

Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders

From intestinal dysbiosis to alcohol-associated liver disease

Modulating the Intestinal Microbiota: Therapeutic Opportunities in Liver Disease

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