Aryl Hydrocarbon Receptor Deficiency in Intestinal Epithelial Cells Aggravates Alcohol-Related Liver Disease

Qian, Minyi; Li, Jun; Zhao, Deyu; Cai, Pengpeng; Pan, Chuyue; Jia, Wenhua; Gao, Yingsheng; Zhang, Yufei; Zhang, Nan; Zhang, Yinan; Zhang, Quan; Wu, Dalei; Shan, Cheng-Jie; Zhang, Meiling; Schnabl, Bernd; Yang, Song; Shen, Xu; Wang, Lirui

doi:10.1016/j.jcmgh.2021.08.014

Cited by 40 publications

(35 citation statements)

References 75 publications

(126 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The sequencing and analysing steps were previously described (Liu et al, 2020; Qian et al, 2021). All the sequencing procedures were performed at Novogene Technology Co., Ltd. (Beijing, China).…”

Section: Methodsmentioning

confidence: 99%

Amlodipine, an anti‐hypertensive drug, alleviates non‐alcoholic fatty liver disease by modulating gut microbiota

Yang

Zhao

Qian

et al. 2022

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

Background and Purpose Non‐alcoholic fatty liver disease (NAFLD) represents a severe public health problem. It often coexists with hypertension in the context of metabolic syndrome. We investigated the effects of amlodipine on NAFLD combined with hypertension and investigated the underlying mechanism/s. Experimental Approach Mice were fed with high‐fat diet (HFD) and 0.05% N‐nitro‐L‐arginine methylester sterile water to induce NAFLD with hypertension. Gut microbiota composition and function were assessed by 16S ribosomal DNA and metagenomic sequencing. Untargeted metabolome profiles were applied to identify differential metabolites in mice caecum. Key Results Amlodipine besylate and amlodipine aspartate significantly decreased liver injury and hepatic steatosis, and improved lipid metabolism with a concomitant reduction in the expression of lipogenic genes in mice with NAFLD and hypertension. Mechanistically, amlodipine besylate and amlodipine aspartate have potential to restore intestinal barrier integrity and improve antimicrobial defence, along with the elevated abundances of Akkermansia, Bacteroides and Lactobacillus. Noteworthily, the gut microbiota in amlodipine besylate‐ and amlodipine aspartate‐treated mice had higher abundance of functional genes involved in taurine and hypotaurine metabolism. Consistently, the strengthened taurine and hypotaurine metabolism was confirmed by untargeted metabolome analysis. Based on the correlation and causal analysis, the altered gut microbiota composition and the enhancement of taurine and hypotaurine metabolism may synergistically decreased alanine aminotransferase, liver triglycerides, lipogenic genes and plasma cholesterol in HFD‐fed hypertensive mice. Conclusion and Implications Amlodipine besylate and amlodipine aspartate exert multifactorial improvements in NAFLD and hypertension by modulating gut microbiota. They may serve as promising therapeutic agents for treating these diseases.

show abstract

Section: Methodsmentioning

confidence: 99%

Amlodipine, an anti‐hypertensive drug, alleviates non‐alcoholic fatty liver disease by modulating gut microbiota

Yang

Zhao

Qian

et al. 2022

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…IAA supplementation, as a microbial-derived ligand of AhR, protects mice from ethanol-induced liver steatohepatitis by preventing bacterial translocation to liver ( 49 ). Intestinal epithelial cell-specific Ahr knockout exacerbates ethanol-induced liver injury through promoting the translocation of Helicobacter hepaticus and Helicobacter ganmani to liver ( 74 ). Ficz (6-formyllindolo (3, 2-B) carbazole), an AhR agonist, reduces ALD liver injury with similar effects to prebiotics.…”

Section: Mechanisms Of Intestinal Dysbiosis In the Development Of Aldmentioning

confidence: 99%

The Role of Gut Bacteria and Fungi in Alcohol-Associated Liver Disease

et al. 2022

View full text Add to dashboard Cite

Cirrhosis and liver cancer caused by alcohol-associated liver disease (ALD) are serious threats to people's health. In addition to hepatic cell apoptosis and liver inflammation caused by oxidative stress during alcohol metabolism, intestinal microbiota disorders are also involved in the onset and development of ALD. Ethanol and its' oxidative and non-oxidative metabolites, together with dysbiosis-caused-inflammation, destroys the intestinal barrier. Changes of several microbial metabolites, such as bile acids, short-chain fatty acids, and amino acid, are closely associated with gut dysbiosis in ALD. The alcohol-caused dysbiosis can further influence intestinal barrier-related proteins, such as mucin2, bile acid-related receptors, and aryl hydrocarbon receptor (AhR), and these abnormal changes also participate in the injury of the intestinal barrier and hepatic steatosis. Gut-derived bacteria, fungi, and their toxins, such as lipopolysaccharide (LPS) and β-glucan translocate into the liver through the damaged intestinal barrier and promote the progression of inflammation and fibrosis of ALD. Thus, the prevention of alcohol-induced disruption of intestinal permeability has a beneficial effect on ALD. Currently, multiple therapeutic treatments have been applied to restore the gut microbiota of patients with ALD. Fecal microbial transplantation, probiotics, antibiotics, and many other elements has already shown their ability of restoring the gut microbiota. Targeted approaches, such as using bacteriophages to remove cytolytic Enterococcus faecalis, and supplement with Lactobacillus, Bifidobacterium, or boulardii are also powerful therapeutic options for ALD.

show abstract

“…There are several important findings in the study by Qian et al 8 that need further investigation to determine their significance in ALD. Although intraperitoneal administration of IBA alone induced liver injury, it is not clear whether intestinal IBA can reach the liver.…”

mentioning

confidence: 96%

“…In this issue of Cellular and Molecular Gastroenterology and Hepatology , by using intestinal epithelial cell (IEC)-specific Ahr knockout mice ( Ahr ΔIEC ), Qian et al 8 demonstrated that AHR signaling in IEC plays an important role in ameliorating ALD. They found that ethanol consumption in mice and humans reduced intestinal expression of AHR.…”

mentioning

confidence: 99%

“…The importance of the work by Qian et al 8 goes beyond intestinal AHR; understanding how ethanol disrupts the vital crosstalk between the gut microbiota, intestine, and liver is essential to discover druggable therapeutic targets for ALD. Previous studies have demonstrated that the alteration of intestinal microbiota by fecal microbiota transplantation, pectin supplementation, or bacteriophage targeting of cytolytic Enterococcus faecalis show preclinical (and potentially clinical) promise in ALD.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Interplay of Gut Microbes and Aryl Hydrocarbon Receptor in Alcohol-Associated Liver Disease

Mackowiak

Gao

2022

Cellular and Molecular Gastroenterology and Hepatology

View full text Add to dashboard Cite

Aryl Hydrocarbon Receptor Deficiency in Intestinal Epithelial Cells Aggravates Alcohol-Related Liver Disease

Cited by 40 publications

References 75 publications

Amlodipine, an anti‐hypertensive drug, alleviates non‐alcoholic fatty liver disease by modulating gut microbiota

Amlodipine, an anti‐hypertensive drug, alleviates non‐alcoholic fatty liver disease by modulating gut microbiota

The Role of Gut Bacteria and Fungi in Alcohol-Associated Liver Disease

Interplay of Gut Microbes and Aryl Hydrocarbon Receptor in Alcohol-Associated Liver Disease

Contact Info

Product

Resources

About