Gut dysbiosis as a driver in alcohol-induced liver injury

Fairfield, Bradley; Schnabl, Bernd

doi:10.1016/j.jhepr.2020.100220

Cited by 67 publications

(68 citation statements)

References 43 publications

(216 reference statements)

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“…The intestinal microbiota contains bacteria, archaea, viruses and fungi. Changes in the bacterial microbiota in patients with alcohol use disorder and ALD have been well characterized and described elsewhere in great detail [27]. The importance of the intestinal microbiota for ALD has been demonstrated in several preclinical and clinical studies.…”

Section: Impact Of the Gut On Alcohol-related Liver Disease Progression And Alcoholic Hepatitismentioning

confidence: 99%

Liver specific, systemic and genetic contributors to alcohol-related liver disease progression

et al. 2022

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Alcohol-related liver disease (ALD) impacts millions of patients worldwide each year and the numbers are increasing. Disease stages range from steatosis via steatohepatitis and fibrosis to cirrhosis, severe alcohol-associated hepatitis and liver cancer. ALD is usually diagnosed at an advanced stage of progression with no effective therapies. A major research goal is to improve diagnosis, prognosis and also treatments for early ALD. This however needs prioritization of this disease for financial investment in basic and clinical research to more deeply investigate mechanisms and identify biomarkers and therapeutic targets for early detection and intervention. Topics of interest are communication of the liver with other organs of the body, especially the gut microbiome, the individual genetic constitution, systemic and liver innate inflammation, including bacterial infections, as well as fate and number of hepatic stellate cells and the composition of the extracellular matrix in the liver. Additionally, mechanical forces and damaging stresses towards the sophisticated vessel system of the liver, including the especially equipped sinusoidal endothelium and the biliary tract, work together to mediate hepatocytic import and export of nutritional and toxic substances, adapting to chronic liver disease by morphological and functional changes. All the aforementioned parameters contribute to the outcome of alcohol use disorder and the risk to develop advanced disease stages including cirrhosis, severe alcoholic hepatitis and liver cancer. In the present collection, we summarize current knowledge on these alcohol-related liver disease parameters, excluding the aspect of inflammation, which is presented in the accompanying review article by Lotersztajn and colleagues.

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Section: Impact Of the Gut On Alcohol-related Liver Disease Progression And Alcoholic Hepatitismentioning

confidence: 99%

Liver specific, systemic and genetic contributors to alcohol-related liver disease progression

et al. 2022

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“…In liver cirrhosis, bacterial overgrowth of the upper intestine has been demonstrated in many studies ( Gurusamy et al, 2021 ), i.e., bacterial biotransfomation of bile acids can already take place in the small intestine. In cirrhosis of the liver, it is not only the bacterial overgrowth of the upper intestinal tract that accompanies disease, but also a dysbiosis ( Qin et al, 2014 ; Arab et al, 2018 ; Fairfield and Schnabl, 2021 ) that takes place mainly in the large bowel. The major phyla in the colon in healthy individuals are Firmicutes and Bacteroidetes as well as Proteobacteria ( Bajaj et al, 2018 ; Haran and McCormick, 2021 ).…”

Section: Intestinementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In addition to initial chronic liver inflammation causing alterations in the intrahepatic blood flow, the intestine has become a focus of pathophysiologic consideration in recent years. Dysbiosis and a disturbed intestinal barrier allow the translocation of molecules, microorganisms, or their products into the interior of the body, where they act as inflammatory stimuli, especially within the liver (Fairfield and Schnabl, 2021). Here, we would like to deal mainly with one group of molecules within these complex systems, namely bile acids (BA) and their possible role in the development of changes in hemodynamics in the context of liver cirrhosis with a focus on the extrahepatic vessels.…”

Section: Introductionmentioning

confidence: 99%

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Bile Acids, Liver Cirrhosis, and Extrahepatic Vascular Dysfunction

et al. 2021

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The bile acid pool with its individual bile acids (BA) is modulated in the enterohepatic circulation by the liver as the primary site of synthesis, the motility of the gallbladder and of the intestinal tract, as well as by bacterial enzymes in the intestine. The nuclear receptor farnesoid X receptor (FXR) and Gpbar1 (TGR5) are important set screws in this process. Bile acids have a vasodilatory effect, at least according to in vitro studies. The present review examines the question of the extent to which the increase in bile acids in plasma could be responsible for the hyperdynamic circulatory disturbance of liver cirrhosis and whether modulation of the bile acid pool, for example, via administration of ursodeoxycholic acid (UDCA) or via modulation of the dysbiosis present in liver cirrhosis could influence the hemodynamic disorder of liver cirrhosis. According to our analysis, the evidence for this is limited. Long-term studies on this question are lacking.

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“…Further studies have shown additional qualitative changes in 16S rRNA analysis of bacterial species, including a relative increase in Proteobacteria and a decrease in Bacteriodaceae , however overall alpha diversity remains stable. Increasing burden of alcohol use with concomitant liver fibrosis or cirrhosis results in further changes in the microbiome, resulting in major metabolic consequences affecting intestinal cells and systemic pathways ( Fairfield and Schnabl, 2021 ). Analysis of stool specimens of patients with cirrhosis and alcoholic hepatitis demonstrate a decrease in SCFA producing bacteria, with an increase in potentially pathogenic bacteria, such as Enterovaeteriaceae, Streptococcaceae, Veillonellaceae, and Prevontellaceae .…”

Section: Alcohol—molecular Mechanisms Of Local and Systemic Effectsmentioning

confidence: 99%

Dietary Patterns and Associated Microbiome Changes that Promote Oncogenesis

Ibragimova

Ramachandran

Ali

et al. 2021

Front. Cell Dev. Biol.

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The recent increases in cancer incidences have been linked to lifestyle changes that result in obesity and metabolic syndrome. It is now evident that these trends are associated with the profound changes that occur in the intestinal microbiome, producing altered microbial population signatures that interact, directly or indirectly, with potentially pro-carcinogenic molecular pathways of transcription, proliferation, and inflammation. The effects of the entire gut microbial population on overall health are complex, but individual bacteria are known to play important and definable roles. Recent detailed examinations of a large number of subjects show a tight correlation between habitual diets, fecal microbiome signatures, and markers of metabolic health. Diets that score higher in healthfulness or diversity such as plant-based diets, have altered ratios of specific bacteria, including an increase in short-chain fatty acid producers, which in turn have been linked to improved metabolic markers and lowered cancer risk. Contrarily, numerous studies have implicated less healthy, lower-scoring diets such as the Western diet with reduced intestinal epithelial defenses and promotion of specific bacteria that affect carcinogenic pathways. In this review, we will describe how different dietary patterns affect microbial populations in the gut and illustrate the subsequent impact of bacterial products and metabolites on molecular pathways of cancer development, both locally in the gut and systemically in distant organs.

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Gut dysbiosis as a driver in alcohol-induced liver injury

Cited by 67 publications

References 43 publications

Liver specific, systemic and genetic contributors to alcohol-related liver disease progression

Liver specific, systemic and genetic contributors to alcohol-related liver disease progression

Bile Acids, Liver Cirrhosis, and Extrahepatic Vascular Dysfunction

Dietary Patterns and Associated Microbiome Changes that Promote Oncogenesis

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