Intestinal HIF-1α deletion exacerbates alcoholic liver disease by inducing intestinal dysbiosis and barrier dysfunction

Shao, Tuo; Zhao, Cuiqing; Li, Fengyuan; Gu, Zelin; Liu, Limimg; Zhang, Lihua; Wang, Yuhua; He, Liqing; Liu, Yunhuan; Liu, Qi; Chen, Yiping; Donde, Hridgandh; Wang, Rui; Jala, Venkatakrishna R.; Barve, Shirish; Chen, Shaoyu; Zhang, Xiang; Chen, Yongping; McClain, Craig J.

doi:10.1016/j.jhep.2018.05.021

Cited by 172 publications

(140 citation statements)

References 61 publications

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“…27 Recently, probiotics have been used as a kind of functional microbes, these have good physiological and biochemical functions for humans, and some researchers have demonstrated that probiotics can effectively attenuate alcoholic liver injury. [32][33][34][35] Forsyth et al, showed the correlation of ALD with oxidative stress and pointed out that LGG could maintain intestinal barrier function by reducing alcohol-oxidative stress and improve the alcoholic fatty liver disease. 36 In previous studies, we demonstrated that…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus rhamnosus Granules Dose-Dependently Balance Intestinal Microbiome Disorders and Ameliorate Chronic Alcohol-Induced Liver Injury

Wang

et al. 2020

Journal of Medicinal Food

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As the functions of Lactobacilli become better understood, there are increasing numbers of applications for Lactobacillus products. Previously, we have demonstrated that Lactobacillus rhamnosus GG (LGG) can prevent alcoholic liver injury. LGG granules were produced by fluid bed granulation with a media composed of starch, skimmed milk powder, whey powder, microcrystalline cellulose and maltose, and LGG fermented liquid that comprised 30-50% of the total weight. We found LGG granules dose-dependently protected against chronic alcoholic liver disease. When alcohol was consumed for 8 weeks with LGG treatment during the last 2 weeks, we demonstrated that the dose dependence of LGG granules can improve alcoholinduced liver injury through decreasing the levels of lipopolysaccharide and tumor necrosis factor-a in serum and prevent liver steatosis by suppressing triglyceride, free fatty acid, and malondialdehyde production in liver. Alcohol feeding caused a decline in the number of both Lactobacillus and Bifidobacterium, with a proportional increase in the number of Clostridium perfringens in ileum, and expansion of the Gram-negative bacteria Proteobacteria, Campylobacterales, and Helicobacter in cecum. However, LGG granule treatment restored the content of these microorganisms. In conclusion, LGG granule supplementation can improve the intestinal microbiota, reduce the number of gram-negative bacteria, and ameliorate alcoholic liver injury.

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Section: Discussionmentioning

confidence: 99%

Lactobacillus rhamnosus Granules Dose-Dependently Balance Intestinal Microbiome Disorders and Ameliorate Chronic Alcohol-Induced Liver Injury

Wang

et al. 2020

Journal of Medicinal Food

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“…Because of the gut-liver circulation via the gut-microbiota-liver axis, nutrients, bacterial products/toxins and metabolites from the gut enters the liver, which play important roles in the progression of liver disease (Wiest et al, 2017). Previous studies indicate that compositional changes of the gut microbiota are closely related to chronic liver diseases, such as non-alcoholic fatty liver disease (NAFLD) (Bibbò et al, 2018;Hoyles et al, 2018;Ponziani et al, 2018), non-alcoholic steatohepatitis (NASH) (Yamada et al, 2017;Bomhof et al, 2018;Ye et al, 2018), alcoholic liver disease (ALD) (Hartmann et al, 2018;Shao et al, 2018;Stärkel et al, 2018), hepatic encephalopathy (HE) (Tilg et al, 2016;Mancini et al, 2018), cirrhosis (Garcia-Tsao and Wiest, 2004;Bajaj et al, 2018a;Guo et al, 2018), hepatocellular carcinoma (HCC) (Zamparelli et al, 2017), and HBV infection. Increasing evidence suggests that the gut microbiota has evolved as a new important player in the pathogenesis of hepatitis B virus-induced chronic liver disease.…”

Section: Introductionmentioning

confidence: 99%

Featured Gut Microbiomes Associated With the Progression of Chronic Hepatitis B Disease

et al. 2020

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“…Under normal circumstances, translocating pathogens will be endocytosed within the lamina propria and mesenteric lymph nodes ( 33 ). However, if the host mucosal immune system is compromised, these defense mechanisms may fail, thus permitting the evasion and survival of bacteria at distant, extraintestinal sites ( 62 , 63 ). Perturbed gut integrity and permeability may allow pathogens translocate into the circulation, which can increase the host’s susceptibility to various types of diseases by inducing chronic or acute inflammatory responses ( 3 ).…”

Section: Discussionmentioning

confidence: 99%

Intestinal Barrier Breakdown and Mucosal Microbiota Disturbance in Neuromyelitis Optical Spectrum Disorders

Chu

Tan

et al. 2020

Front. Immunol.

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Background and Purpose The mechanism underlying the pathology of neuromyelitis optica spectrum disorders (NMOSD) remains unclear even though antibodies to the water channel protein aquaporin-4 (AQP4) on astrocytes play important roles. Our previous study showed that dysbiosis occurred in the fecal microbiota of NMOSD patients. In this study, we further investigated whether the intestinal barrier and mucosal flora balance are also interrupted in NMOSD patients. Methods Sigmoid mucosal biopsies were collected by endoscopy from six patients with NMOSD and compared with samples from five healthy control (HC) individuals. These samples were processed for electron microscopy and immunohistochemistry to investigate changes in ultrastructure and in the number and size of intestinal inflammatory cells. Changes in mucosal flora were also analyzed by high-throughput 16S ribosomal RNA gene amplicon sequencing. Results The results from bacterial rRNA gene sequencing showed that bacterial diversity was decreased, but Streptococcus and Granulicatella were abundant in the colonic mucosa specimens of NMOSD patients compared to the HC individuals. The intercellular space between epithelia of the colonic mucosa was wider in NMOSD patients compared to the HC subjects ( p < 0.01), and the expression of tight junction proteins [occludin, claudin-1 and zonula occludens-1 (ZO-1)] in NMOSD patients significantly decreased compared to that in the HC subjects. We also found numerous activated macrophages with many inclusions within the cytoplasm, mast cells with many particles in their cytoplasm, and enlarged plasma cells with rich developed rough endoplasmic reticulum in the lamina propria of the mucosa of the patients with NMOSD. Quantitative analysis showed that the percentages of small CD38+ and CD138+ cells (plasma cells) were lower, but the percentage of larger plasma cells was higher in NMOSD patients. Conclusion The present study demonstrated that the intestinal barrier was disrupted in the patients with NMOSD, accompanied by dysbiosis and inflammatory activation of the gut. The mucosal microbiota imbalance and inflammatory responses might allow pathogens to cross the damaged intestinal barrier and participate in pathological process in NMOSD. However, further study on the pathological mechanism of NMOSD underlying gut dysbiosis is warranted in the future.

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Intestinal HIF-1α deletion exacerbates alcoholic liver disease by inducing intestinal dysbiosis and barrier dysfunction

Cited by 172 publications

References 61 publications

Lactobacillus rhamnosus Granules Dose-Dependently Balance Intestinal Microbiome Disorders and Ameliorate Chronic Alcohol-Induced Liver Injury

Lactobacillus rhamnosus Granules Dose-Dependently Balance Intestinal Microbiome Disorders and Ameliorate Chronic Alcohol-Induced Liver Injury

Featured Gut Microbiomes Associated With the Progression of Chronic Hepatitis B Disease

Intestinal Barrier Breakdown and Mucosal Microbiota Disturbance in Neuromyelitis Optical Spectrum Disorders

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