Inhibition of miR122a by Lactobacillus rhamnosus GG culture supernatant increases intestinal occludin expression and protects mice from alcoholic liver disease

Toxicology Letters
Haiyang ZhaoWenke Feng

Abstract

Alcoholic liver disease (ALD) has a high morbidity and mortality. Chronic alcohol consumption causes disruption of intestinal microflora homeostasis, intestinal tight junction barrier dysfunction, increased endotoxemia, and eventually liver steatosis/steatohepatitis. Probiotic Lactobacillus rhamnosus GG (LGG) and the bacteria-free LGG culture supernatant (LGGs) have been shown to promote intestinal epithelial integrity and protect intestinal barrier function in ALD. However, little is known about how LGGs mechanistically works to increase intestinal tight junction proteins. Here we show that chronic ethanol exposure increased intestinal miR122a expression, which decreased occludin expression leading to increased intestinal permeability. Moreover, LGGs supplementation decreased ethanol-elevated miR122a level and attenuated ethanol-induced liver injury in mice. Similar to the effect of ethanol exposure, overexpression of miR122a in Caco-2 monolayers markedly decreased occludin protein levels. In contrast, inhibition of miR122a increased occludin expression. We conclude that LGGs supplementation functions in intestinal integrity by inhibition of miR122a, leading to occludin restoration in mice exposed to chronic ethanol.

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Citations

Nov 28, 2015·Biomolecules·Sathish Kumar NatarajanJustin L Mott
Feb 4, 2016·Gastroenterology Research and Practice·Fengyuan LiWenke Feng
Aug 24, 2016·Cellular Microbiology·Toni M FörsterBernhard Hube
Jun 24, 2017·Pharmacology & Therapeutics·Ming-Jiang XuBin Gao
Oct 1, 2016·American Journal of Physiology. Gastrointestinal and Liver Physiology·Sena BluemelBernd Schnabl
Aug 30, 2018·Bioscience, Biotechnology, and Biochemistry·Jun-Juan WangYuan-Yuan Li
Jun 5, 2019·International Journal of Molecular Sciences·Ling-Zu KongTaeho Kwon
Sep 14, 2019·Applied Microbiology and Biotechnology·Tony J FangWen-Hsin Lin
Aug 17, 2017·Biomolecules·Lauren G PooleGavin E Arteel
Jan 11, 2019·Microbiology and Molecular Biology Reviews : MMBR·Aislinn D Rowan-NashPeter Belenky
Jul 3, 2019·Gastroenterology Research and Practice·Zelin GuYuhua Wang
Sep 24, 2020·Journal of Leukocyte Biology·Niya L MorrisMashkoor A Choudhry
Dec 7, 2018·Disease Models & Mechanisms·Matthew T PereiraLaura Palanker Musselman
Feb 12, 2019·Journal of Clinical Gastroenterology·Lucio Capurso
Apr 17, 2019·Microorganisms·Charlotte SegersFelice Mastroleo
Dec 10, 2020·International Journal of Food Sciences and Nutrition·Chu-Han HuangChen-Meng Kuan
Nov 25, 2019·The Journal of Nutritional Biochemistry·Qi LiuWenke Feng
Feb 13, 2021·Journal of Leukocyte Biology·Niya L Morris, Mashkoor A Choudhry
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Dec 1, 2019·Liver Research·Fengyuan LiWenke Feng
Jan 17, 2019·Gene Expression·Tirthadipa Pradhan-Sundd, Satdarshan Pal Monga

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