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

Abstract

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 non-alcoholic 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.

Keywords: Non-steroidal anti-inflammatory drugs; Intestinal barrier; Intestinal permeability; Non-steroidal anti-inflammatory drugs - enteropathy; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Microbiota; Metabolic syndrome; Proton pump inhibitors; Endotoxaemia

Core tip: Among the gastro-intestinal effects, in non-steroidal anti-inflammatory drugs (NSAIDs) users, those of the lower tract seem to be rising. NSAIDs enteropathy is due to the enterohepatic recycling of drugs, resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites, leading to so called topical effects. The impairment of the intestinal barrier represents the initial damage of NSAIDs enteropathy that leads to the translocation of bacteria and toxic substances of intestinal origin in the portal circulation, promoting an endotoxaemia. This condition, mostly in patients with risk factors for nonalcoholic fatty liver diseas, such as obesity and metabolic syndrome, might lead to liver inflammatory response that could promote the development of nonalcoholic steatohepatitis.