Prophylactic tributyrin treatment mitigates chronic‐binge ethanol‐induced intestinal barrier and liver injury

Cresci, Gail; Glueck, Bryan; McMullen, Megan R.; Wei, Xin; Allende, D.A; Nagy, Laura E.

doi:10.1111/jgh.13731

Cited by 122 publications

(117 citation statements)

References 56 publications

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“…Butyrate is thought to help modulate intestinal barrier integrity by modulating the expression of tight junction proteins and mucin. 52,53 This suggests that encouraging growth of butyrateproducing species could reduce gut permeability and systemic inflammation. Inulin-type fructans promote the production of butyrate in vitro.…”

Section: Alcohol and Gut Metabolomementioning

confidence: 99%

Microbiome as a therapeutic target in alcohol-related liver disease

Sarin

Pande

Schnabl

2019

Journal of Hepatology

197

154

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Alcohol-related liver disease is associated with significant changes in gut microbial composition. The transmissibility of ethanol-induced liver disease has been demonstrated using faecal microbiota transfer in preclinical models. This technique has also led to improved survival in patients with severe alcoholic hepatitis, suggesting that changes in the composition and function of the gut microbiota are causatively linked to alcohol-related liver disease. A major mechanism by which gut microbiota influence the development of alcohol-related liver disease is through a leaky intestinal barrier. This permits translocation of viable bacteria and microbial products to the liver, where they induce and promote inflammation, as well as contribute to hepatocyte death and the fibrotic response. In addition, gut dysbiosis is associated with changes in the metabolic function of the intestinal microbiota, bile acid composition and circulation, immune dysregulation during onset and progression of alcohol-related liver disease. Findings from preclinical and human studies will be used to demonstrate how alcohol causes intestinal pathology and contributes to alcohol-related liver disease and how the latter is self-perpetuating. Additionally, we summarise the effects of untargeted treatment approaches on the gut microbiota, such as diet, probiotics, antibiotics and faecal microbial transplantation in alcohol-related liver disease. We further discuss how targeted approaches can restore intestinal homeostasis and improve alcohol-related liver disease. These approaches are likely to add to the therapeutic options for alcohol-related liver disease independently or in conjunction with steroids. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.Gut microbiota contributes to the development of alcohol-related liver disease via different mechanisms. The altered gut bacteria in alcoholic hepatitis lead to suppression of the immune system, increase in hepatic inflammation and changes in microbial metabolites.

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Section: Alcohol and Gut Metabolomementioning

confidence: 99%

Microbiome as a therapeutic target in alcohol-related liver disease

Sarin

Pande

Schnabl

2019

Journal of Hepatology

197

154

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“…84 Supplementation with butyrate (tributyrin) mitigated alcohol-induced gut barrier disruption and liver injury both in acute and chronic alcohol-intoxicated mice. 169,170 …”

Section: Targeting the Leaking Gut To Treat Aldmentioning

confidence: 99%

Targeting the gut barrier for the treatment of alcoholic liver disease

Zhou

Zhong

2017

Liver Research

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Alcohol consumption remains one of the predominant causes of liver disease and liver-related death worldwide. Intriguingly, dysregulation of the gut barrier is a key factor promoting the pathogenesis of alcoholic liver disease (ALD). A functional gut barrier, which consists of a mucus layer, an intact epithelial monolayer and mucosal immune cells, supports nutrient absorption and prevents bacterial penetration. Compromised gut barrier function is associated with the progression of ALD. Indeed, alcohol consumption disrupts the gut barrier, increases gut permeability, and induces bacterial translocation both in ALD patients and in experimental models with ALD. Moreover, alcohol consumption also causes enteric dysbiosis with both numerical and proportional perturbations. Here, we review and discuss mechanisms of alcohol-induced gut barrier dysfunction to better understand the contribution of the gut-liver axis to the pathogenesis of ALD. Unfortunately, there is no effectual Food and Drug Administration-approved treatment for any stage of ALD. Therefore, we conclude with a discussion of potential strategies aimed at restoring the gut barrier in ALD. The principle behind antibiotics, prebiotics, probiotics and fecal microbiota transplants is to restore microbial symbiosis and subsequently gut barrier function. Nutrient-based treatments, such as dietary supplementation with zinc, niacin or fatty acids, have been shown to regulate tight junction expression, reduce intestinal inflammation, and prevent endotoxemia as well as liver injury caused by alcohol in experimental settings. Interestingly, saturated fatty acids may also directly control the gut microbiome. In summary, clinical and experimental studies highlight the significance and efficacy of the gut barrier in treating ALD.

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“…Furthermore, unlike sodium butyrate, TB does not have the butyrate‐distinctive offensive odor and is a liquid at the normal temperature, thus TB could be a more practical supplement to the MR compared to sodium butyrate. In mice, supplementation of TB protected both the intestinal barrier and liver from injury caused by the combined chronic‐binge ethanol exposure (Cresci et al, ). However, to our knowledge, effects of TB supplementation to the MR on growth and health performance, blood metabolite and GLP‐2 concentrations were not investigated in dairy calves.…”

Section: Introductionmentioning

confidence: 99%

The effect of tributyrin supplementation to milk replacer on plasma glucagon‐like peptide 2 concentrations in pre‐weaning calves

Inabu

Murayama

Inouchi

et al. 2019

Animal Science Journal

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The objective of this study was to evaluate the effect of tributyrin (TB) supplementation to milk replacer (MR) on performance, health, and blood concentrations of metabolite and glucagon‐like peptide (GLP‐2) in pre‐weaning calves. Twenty Holstein heifer calves were raised on an intensified nursing program using MR supplemented with either palm oil (CON) or TB (TB) at 0.3% (as fed basis) for 7 weeks starting 1 week after birth. Calves were fed a calf starter and kleingrass from the beginning of the study. Blood samples were obtained weekly to measure blood glucose, serum β‐hydroxybutyric acid (BHBA), insulin‐like growth factor 1 (IGF‐1), and plasma GLP‐2 concentrations. Starter DMI and metabolizable energy (ME) intake were lower in TB calves at 46, 47, from 49 to 55 days after birth compared with the CON calves. However, any growth parameters were not affected by TB treatment. Blood glucose, serum BHBA, and IGF‐1 concentrations were not affected by TB supplementation. On the other hand, mean plasma GLP‐2 concentration among whole experimental period was higher for TB (0.60 ng/ml) compared with CON (0.41 ng/ml). In conclusion, feeding MR supplemented with TB increases plasma GLP‐2 concentration, which might counterbalance the growth performance of TB calves despite the decreased ME intake.

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Prophylactic tributyrin treatment mitigates chronic‐binge ethanol‐induced intestinal barrier and liver injury

Cited by 122 publications

References 56 publications

Microbiome as a therapeutic target in alcohol-related liver disease

Microbiome as a therapeutic target in alcohol-related liver disease

Targeting the gut barrier for the treatment of alcoholic liver disease

The effect of tributyrin supplementation to milk replacer on plasma glucagon‐like peptide 2 concentrations in pre‐weaning calves

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