scholarly journals Dietary Copper Plays an Important Role in Maintaining Intestinal Barrier Integrity During Alcohol-Induced Liver Disease Through Regulation of the Intestinal HIF-1α Signaling Pathway and Oxidative Stress

2020 ◽  
Vol 11 ◽  
Author(s):  
Hongwei Lin ◽  
Dazhi Chen ◽  
Qianjing Du ◽  
Tongtong Pan ◽  
Hanxiao Tu ◽  
...  
Gut ◽  
2017 ◽  
Vol 67 (5) ◽  
pp. 891-901 ◽  
Author(s):  
Christoph Grander ◽  
Timon E Adolph ◽  
Verena Wieser ◽  
Patrick Lowe ◽  
Laura Wrzosek ◽  
...  

ObjectiveAlcoholic liver disease (ALD) is a global health problem with limited therapeutic options. Intestinal barrier integrity and the microbiota modulate susceptibility to ALD. Akkermansia muciniphila, a Gram-negative intestinal commensal, promotes barrier function partly by enhancing mucus production. The aim of this study was to investigate microbial alterations in ALD and to define the impact of A. muciniphila administration on the course of ALD.DesignThe intestinal microbiota was analysed in an unbiased approach by 16S ribosomal DNA (rDNA) sequencing in a Lieber-DeCarli ALD mouse model, and faecal A. muciniphila abundance was determined in a cohort of patients with alcoholic steatohepatitis (ASH). The impact of A. muciniphila on the development of experimental acute and chronic ALD was determined in a preventive and therapeutic setting, and intestinal barrier integrity was analysed.ResultsPatients with ASH exhibited a decreased abundance of faecal A. muciniphila when compared with healthy controls that indirectly correlated with hepatic disease severity. Ethanol feeding of wild-type mice resulted in a prominent decline in A. muciniphila abundance. Ethanol-induced intestinal A. muciniphila depletion could be restored by oral A. muciniphila supplementation. Furthermore, A. muciniphila administration when performed in a preventive setting decreased hepatic injury, steatosis and neutrophil infiltration. A. muciniphila also protected against ethanol-induced gut leakiness, enhanced mucus thickness and tight-junction expression. In already established ALD, A. muciniphila used therapeutically ameliorated hepatic injury and neutrophil infiltration.ConclusionEthanol exposure diminishes intestinal A. muciniphila abundance in both mice and humans and can be recovered in experimental ALD by oral supplementation. A. muciniphila promotes intestinal barrier integrity and ameliorates experimental ALD. Our data suggest that patients with ALD might benefit from A. muciniphila supplementation.


2021 ◽  
Author(s):  
HuiYuan Xu ◽  
LeiLei Yang ◽  
YuMei Huang ◽  
ChangPing Li

Abstract This study was aimed to investigate the impact of probiotics on regulating the ROS/JNK signaling pathway their underlying mechanism of action in the treatment of nonalcoholic fatty liver disease. For this purpose, male C57BL/6 mice were randomly divided into three groups: control, probiotics, and model groups. Methionine and choline deficiency (MCD) diets were fed for four weeks to establish a NAFLD mouse model. Serum levels of ALT, AST, TC, and TG were detected. Moreover, the pathological changes of the liver and ileum tissues were observed by hematoxylin and eosin (H&E) staining, and the content of reactive oxygen species (ROS) in liver tissues was determined. In addition, the levels of D-lactic acid and plasma and small intestine diamine oxidase were measured to evaluate the effects of probiotics on the intestinal tract of NAFLD mice. The expression levels of p-JNK, Bax, and Caspase-3 were established to analyze the regulatory mechanism of probiotics on the JNK signaling pathway. We found that probiotics improve liver function, repair intestinal barrier and significantly suppressed oxidative stress, JNK phosphorylation. Moreover, the application of probiotics regulated the expression of signaling pathway-related proteins and promoted the intestinal barrier function repair and decreased intestinal permeability. The data above suggest that probiotics alleviate NAFLD, whose mechanism might be associated with the regulation of ROS/JNK signaling pathway and the suppression of oxidative stress and apoptosis.


2021 ◽  
Vol 12 (7) ◽  
pp. 2950-2961
Author(s):  
Maryam Ershad ◽  
Mark K. Shigenaga ◽  
Brian Bandy

Excess dietary fat, and associated bile acids, can impair intestinal barrier integrity, produce intestinal or systemic inflammation and promote tumorigenesis.


2021 ◽  
pp. jim-2020-001437
Author(s):  
Ming Chen ◽  
Minghui Li ◽  
Na Zhang ◽  
Wenwen Sun ◽  
Hui Wang ◽  
...  

This study was aimed to investigate the effects of miR-218-5p on the proliferation, apoptosis, autophagy, and oxidative stress of rheumatoid arthritis synovial fibroblasts (RASFs), and the related mechanisms. Quantitative reverse transcription–PCR showed that the expression of miR-218-5p in rheumatoid arthritis synovial tissue was significantly higher than that in healthy synovial tissue. Compared with healthy synovial fibroblasts, miR-218-5p expression was obviously upregulated in RASFs, while KLF9 protein expression was markedly downregulated. Mechanistically, miR-218-5p could directly bind to the 3′ untranslated region of KLF9 to inhibit the expression of KLF9. Additionally, transfection of miR-218-5p small interfering RNA (siRNA) inhibited the proliferation but promoted apoptosis and autophagy of RASFs. Simultaneously, miR-218-5p silencing reduced reactive oxygen species and malondialdehyde levels and increased superoxide dismutase and glutathione peroxidase activity to improve oxidative stress in RASFs. More importantly, the introduction of KLF9 siRNA reversed the effects of miR-218-5p siRNA transfection on RASF proliferation, apoptosis, autophagy, and oxidative stress. What is more, silencing miR-218-5p inhibited the activation of JAK2/STAT3 signaling pathway by targeting KLF9. Collectively, knockdown of miR-218-5p could regulate the proliferation, apoptosis, autophagy and oxidative stress of RASFs by increasing the expression of KLF9 and inhibiting the activation of the JAK2/STAT3 signaling pathway, which may provide a potential target for the mechanism research of RA.


Gut Microbes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1946368
Author(s):  
Angélica Cruz-Lebrón ◽  
Ramona Johnson ◽  
Claire Mazahery ◽  
Zach Troyer ◽  
Samira Joussef-Piña ◽  
...  

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