Intestinally derived bacterial products stimulate development of nonalcoholic steatohepatitis. (March 2019)

• Record Type: Journal Article
• Authors: Dornas, Waleska; Lagente, Vincent
• Is Part Of: Pharmacological research. Volume 141(2019)
• Page Start: 418
• Page End: 428
• Publication Date: 2019-03
• Subjects: α-SMA alpha-smooth muscle -- AC alcoholic cirrhosis -- ALT alanine aminotransferase -- ApoE apopoliprotein E -- AST aspartate aminotransferase -- BDL bile duct ligation -- BMI body mass index -- CDAA choline-deficient amino acid-defined -- CDHF choline-deficient high-fat -- CD14 cluster of differentiation 14 -- COL Iα1 collagen type Iα1 -- COX-2 cyclooxygenase-2 -- CRP C-reactive protein -- DAMPs damage associated molecular patterns -- DSS dextran sulfate sodium -- FOS fructo-oligosaccharides -- FXR farnesoid X receptor -- GalN d-galactosamine -- GI gastrointestinal -- GLP-2 glucagon-like peptide 2 -- GPR43 G protein-coupled receptor 43 -- HC high cholesterol -- HCal high caloric -- HCV hepatitis C virus -- HF high fat -- HFr high fructose -- HNE 4-hydroxynonenal -- HOMA Homeostasis model assessment–estimated insulin resistance index -- HSCs Hepatic stellate cells -- IL interleukin -- iNOS inducible nitric oxide synthase -- IR insulin resistance -- KCs kupffer cells -- KO knockout -- LEC liver endothelial cell -- LKO liver-specific knockout mice -- LPS lipopolysaccharide -- MCD methionine/choline-deficient -- MDA malondialdehyde -- MD2 TLR4/myeloid differentiation protein 2 -- MMP matrix metalloproteinase -- MyD88 myeloid differentiation primary-response gene 88 -- MFB myofibroblast -- NAFLD nonalcoholic fatty liver disease -- NASH nonalcoholic steatohepatitis -- NF-κb factor nuclear kappa B -- NLRP nucleotide-binding domain leucine-rich repeat protein -- NLRs NOD-like receptors -- NOD nucleotide oligomerization domain -- OFS oligofructose -- PAMPs pathogen-associated molecular patterns -- PPAR peroxisome proliferator-activated receptor -- PUFAs polyunsaturated fatty acids -- ROS reactive oxygen species -- SCFAs short-chain fatty acids -- SIBO small intestinal bacterial overgrowth -- TG triglyceride -- TGF-β transforming growth factor -- TIMP tissue inhibitor of metalloproteinase -- TLR toll-like receptor -- TNF-α tumor necrosis factor alpha -- VIT vitamin -- VSL#3 probiotic mixture of Streptococcus thermophilus, Lactobacillus/Bifidobacterium species -- WT wild type; Gut microbiota -- Hepatic stellate cell -- Inflammation -- Lipopolysaccharide -- Liver fibrosis -- Nonalcoholic steatohepatitis; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2019.01.026
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Fatty livers are susceptible to factors that cause inflammation and fibrosis, but fat deposition and the inflammatory response can be dissociated. While nonalcoholic fatty liver disease (NAFLD), caused by pathologic fat accumulation inside the liver, can remain stable for several years, in other cases NAFLD progresses to nonalcoholic steatohepatitis (NASH), which is characterized by fat accumulation and inflammation and is not a benign condition. In this review, we discuss the NASH host cells and microbial mechanisms that stimulate inflammation and predispose the liver to hepatocyte injury and fibrotic stages via increased lipid deposition. We highlight the interactions between intestine-derived bacterial products, such as lipopolysaccharide, and nutritional models of NAFLD and/or obese individuals. The results of modulating enteric microbiota suggest that gut-derived endotoxins may be essential determinants of fibrotic progression and regression in NASH.