Microbiota Plays a Key Role in Non-Steroidal Anti-Inflammatory Drug-Induced Small Intestinal Damage

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) damage the small intestine by causing multiple erosions and ulcers. However, to date, no established therapies and prophylactic agents are available to treat such damages. We reviewed the role of intestinal microbiota in NSAID-induced intestinal damage and identified potential therapeutic candidates. Summary: The composition of the intestinal microbiota is an important factor in the pathophysiology of NSAID-induced small intestinal damage. Once mucosal barrier function is disrupted due to NSAID-induced prostaglandin deficiency and mitochondrial malfunction, lipopolysaccharide from luminal gram-negative bacteria and high mobility group box 1 from the injured epithelial cells activate toll-like receptor 4-signaling pathway and nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 inflammasome; this leads to the release of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-1β. Proton pump inhibitors (PPIs) are often used for the prevention of NSAID-induced injuries to the upper gastrointestinal tract. However, several studies indicate that PPIs may induce dysbiosis, which may exacerbate the NSAID-induced small intestinal damage. Our recent research suggests that probiotics and rebamipide could be used to prevent NSAID-induced small intestinal damage by regulating the intestinal microbiota. Key Messages: Intestinal microbiota plays a key role in NSAID-induced small intestinal damage, and modulating the composition of the intestinal microbiota could be a new therapeutic strategy for treating this damage.

Potential Strategies in the Prevention of Nonsteroidal Anti-inflammatory Drugs-Associated Adverse Effects in the Lower Gastrointestinal Tract

“…Accumulating evidences suggest that intestinal bacteria may play a significant role in the pathogenesis of small-bowel dam-age induced by NSAIDs and that enterobacterial translocation into the mucosa represents the first step of a series of events leading to gross lesion formation. 66,67 It has been reported that germ-free mice were resistant to NSAIDs related intestinal damage. 68,69 However, when germ-free mice were colonized with jejunal bacteria from PPI-treated rats, the severity of NSAIDinduced intestinal injury increased.…”

Clinical Utility of Capsule Endoscopy and Double-Balloon Enteroscopy in the Management of Obscure Gastrointestinal Bleeding

“…Proton pump inhibitor may induce dysbiosis of intestinal microbiota and exacerbate the small intestinal damage such as erosions/ulcers. We consider that intestinal microbiota plays a crucial role in NSAID-induced small intestinal damage [9]. Novel therapy modulating the composition of the intestinal microbiota could be developed for such small intestinal damages [10].…”

Intestinal Dysbiosis Secondary to Proton-Pump Inhibitor Use

“…Although most of the interactions between a host and its commensal microbiota and their metabolites are symbiotic, changes in the composition and function of the gut microbiota, called “dysbiosis”, are thought to be associated with various kinds of diseases [1,2]. Intestinal dysbiosis has been demonstrated to be associated with inflammatory bowel disease (IBD) [3,4], irritable bowel syndrome [5], and nonsteroidal anti-inflammatory drugs-induced enteropathy [6]. Moreover, gut dysbiosis has been reported in patients with types 1 and 2 diabetes [7,8], multiple sclerosis [9], autism [10], and rheumatoid arthritis [11].…”