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Autophagy Deficiency in the Liver Altered Pathogenesis of Alcoholic Liver Disease and Profile of Gut Microbiota
Author(s) -
Yan Shengmin,
Khambu Bilon,
Chen Xiaoyun,
Yin XiaoMing
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.126.5
Subject(s) - atg5 , autophagy , gut flora , liver injury , alcoholic liver disease , bile acid , biology , endocrinology , medicine , steatosis , ethanol metabolism , liver disease , metabolism , immunology , biochemistry , cirrhosis , apoptosis
Autophagy is an evolutionarily conserved cellular degradation process that is critical to maintain metabolism homeostasis in the liver. To investigate the role of autophagy in liver diseases, we examined the impact of autophagy deficiency on ethanol‐induced liver injury and the gut‐liver relationship. First, hepatic autophagy deficient mice were challenged with ethanol by either acute or acute‐on‐chronic scheme. Our results demonstrated a protective role of autophagy in ethanol‐induced liver injury in a genetic and an inducible hepatic Atg7 knockout mice. Surprisingly, hepatic Atg5 knockout mice, which had a minor presentation of liver injury, were resistant to acute ethanol treatment, and were actually improved in the liver presentation following the treatment of in the chronic‐plus‐binge regime. A series of ethanol metabolism‐related genes were altered in livers of ethanol‐fed Atg5 Δhep mice, which was accompanied with a faster clearance of plasma ethanol. This may partially explain the seemingly paradoxical observations. Second, gut microbiota was analyzed in fecal samples from hepatic autophagy deficient mice by 16S sequencing. The profile of gut microbiota was altered by hepatic autophagy deficiency with a notable increase of bile acids metabolism related bacteria. In addition to this, significant increase of total bile acids was observed in serum, liver, and feces. Moreover, ileal FXR was activated as increased gene expression of its target genes, including Shp, Fgf15 and Ibabp . Finally, modulation of gut microbiota by antibiotics treatment suppressed ileal FXR activation, increased enterohepatic bile acids pool, and aggravated liver injury in hepatic autophagy‐deficient mice. Collectively, our results indicate that hepatic autophagy has significant impacts on liver homeostasis and gut microbiota. The alteration of gut microbiota in hepatic autophagy deficiency can have in turn notable effects on liver injury. Support or Funding Information This research was partially supported by NIH R01AA021751 (X.‐M.Y.). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .