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

Abstract

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.

Bacteroides acidifaciens in the gut plays a protective role against CD95-mediated liver injury

“…Previous studies showed that Bacteroides protected intestinal barrier function, which had an important influence on liver diseases. 42 HE staining of colonic tissue and FITC-dextran fluorescence detection in the serum indicated that antibiotic treatment or BA and PD intragastric administration did not change intestinal barrier integrity or permeability in the present study. No bacteria were detected in the 16S rRNA analysis of the mouse liver tissue and liver homogenate culture after antibiotic treatment or BA and PD gavage.…”

“…The gut microbiota plays an important regulatory role in many human and mouse liver diseases. 41 , 42 Differences in intestinal flora composition may lead to diversities in the severity of liver diseases in the host. 14 Previous studies identified some bacterial genera that were relevant to autoimmune or alcoholic hepatitis in humans and animals using correlation analysis, such as Faecalibacterium, Veillonella, Akkmensia, Blautia, Parabacteroides and Bacteroides .…”

CONSORT-Characteristics and metabolic phenotype of gut microbiota in NAFLD patients

“…With improvements in living standards, lifestyle changes, and increased obese populations, NAFLD is becoming increasingly common in China. [2] Many studies have confirmed that the gut microbiota affects the disease occurrence and development. [3] The gut of healthy people contains more than 1,000 different bacteria with approximately ten times more number of cells than those making up the entire human body.…”

“…With improvements in living standards, lifestyle changes, and increased obese populations, NAFLD is becoming increasingly common in China. [ 2 ]…”

Recent advances of gut microbiota in chronic kidney disease patients

“…Gut microbial community produces a natural defense barrier and influences physiology, immune function, metabolism and nutrition. A variety of clinical and experimental evidence has indicated that microbial environment has played a key role in health and disease, such as cancers, cardiovascular disease, obesity, diabetic mellitus, hypertension, CKD and non-alcoholic fatty liver disease [40][41][42][43][44][45][46][47][48][49][50][51][52].…”