Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease

• Published in: World journal of gastroenterology : WJG Vol. 23; no. 22; pp. 3954 - 3963
• Main Authors: Utzeri, Erika, Usai, Paolo
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 14.06.2017
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Bacterial Translocation - drug effects; Gastrointestinal Microbiome - drug effects; Humans; Insulin Resistance; Intestinal Diseases - chemically induced; Intestinal Diseases - metabolism; Intestinal Diseases - microbiology; Intestinal Diseases - therapy; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Lipogenesis - drug effects; Liver - drug effects; Liver - metabolism; Liver - microbiology; Non-alcoholic Fatty Liver Disease - chemically induced; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - microbiology; Non-alcoholic Fatty Liver Disease - therapy; Oxidative Stress - drug effects; Permeability; Review; Risk Factors; Tight Junctions - drug effects; Tight Junctions - metabolism; Tight Junctions - microbiology; Weight Gain - drug effects; Intestinal barrier; Endotoxaemia; Microbiota; Nonalcoholic steatohepatitis; Intestinal permeability; Proton pump inhibitors; Nonalcoholic fatty liver disease; Metabolic syndrome; Non-steroidal anti-inflammatory drugs; Non-steroidal anti-inflammatory drugs - enteropathy
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.v23.i22.3954

The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.