Gut Microbiota in NSAID Enteropathy: New Insights From Inside

As a class of the commonly used drugs in clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) can cause a series of adverse events including gastrointestinal injuries. Besides upper gastrointestinal injuries, NSAID enteropathy also attracts attention with the introduction of capsule endoscopy and double balloon enteroscopy. However, the pathogenesis of NSAID enteropathy remains to be entirely clarified. Growing evidence from basic and clinical studies presents that gut microbiota is a critical factor in NSAID enteropathy progress. We have reviewed the recent data about the interplay between gut microbiota dysbiosis and NSAID enteropathy. The chronic medication of NSAIDs could change the composition of the intestinal bacteria and aggravate bile acids cytotoxicity. Meanwhile, NSAIDs impair the intestinal barrier by inhibiting cyclooxygenase and destroying mitochondria. Subsequently, intestinal bacteria translocate into the mucosa, and then lipopolysaccharide released from gut microbiota combines to Toll-like receptor 4 and induce excessive production of nitric oxide and pro-inflammatory cytokines. Intestinal injuries present in the condition of intestinal inflammation and oxidative stress. In this paper, we also have reviewed the possible strategies of regulating gut microbiota for the management of NSAID enteropathy, including antibiotics, probiotics, prebiotics, mucosal protective agents, and fecal microbiota transplant, and we emphasized the adverse effects of proton pump inhibitors on NSAID enteropathy. Therefore, this review will provide new insights into a better understanding of gut microbiota in NSAID enteropathy.

Glycomacropeptide Ameliorates Indomethacin-Induced Enteropathy in Rats by Modifying Intestinal Inflammation and Oxidative Stress

Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is considered a serious and increasing clinical problem without available treatment. Glycomacropeptide (GMP) is a 64-amino acid peptide derived from milk κ-casein with numerous biological activities. The aim of this study was to investigate the protective effect of GMP on NSAID enteropathy in rats. Enteropathy was induced by seven days oral indomethacin administration. Rats were orally GMP treated from seven days previous and during the establishment of the enteropathy model. Changes in metabolism, hematological and biochemical blood alterations, intestinal inflammation and oxidative damage were analyzed. Integrity barrier markers, macroscopic intestinal damage and survival rate were also evaluated. GMP treatment prevented anorexia and weight loss in animals. Furthermore, prophylaxis with GMP ameliorated the decline in hemoglobin, hematocrit, albumin and total protein levels. The treatment had no therapeutic efficacy on the decrease of occludin and mucin (MUC)-2 expression in intestinal tissue. However, GMP markedly decreased neutrophil infiltration, and CXCL1, interleukin-1β and inducible nitric oxide synthase expression. Nitric oxide production and lipid hydroperoxide level in the small intestine were also diminished. These beneficial effects were mirrored by preventing ulcer development and increasing animal survival. These results suggest that GMP may protect against NSAID enteropathy through anti-inflammatory and antioxidant properties.

NSAID enteropathy

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used drugs in the world, and their side effects are very high. First of all, these are NSAID gastropathy, but in the long term, 5070% of NSAIDs cause damage to the small intestine (NSAID enteropathy), sometimes with serious consequences. To date, no drugs have been proposed with proven effectiveness to prevent this side effect. Apparently, this is not due to the fully clarified mechanism of pathogenesis. The most promising is the hypothesis of the participation of individual representatives of microflora in the development of enteropathy. Therefore, modulating the intestinal flora with the help of probiotics can be the basic therapeutic strategy for the prevention and treatment of such damage.

Pharmacological and clinical feature of rebamipide: new therapeutic targets

Rebamipide is a cytoprotector developed in Japan where it has been successfully used for the treatment of stomach diseases for 30 years. Initially discovered effects of the drug included the induction of prostaglandins and the elimination of free oxygen radicals. Recent studies discovered new therapeutic targets of the drug, its new forms that made possible using rebamipid for the treatment of such diseases as NSAID enteropathy, ulcerative colitis, radiation colitis, pouchitis, enteropathy with impaired membrane digestion. It is used in endoscopy, ophthalmology, chemotherapy, rheumatology. The aim of this review is to present current information about the pharmacological and clinical feature of rebamipide and to study its therapeutic potential.

Small intestinal damage associated with the use of nonsteroidal anti-inflammatory drugs

The use of nonsteroidal anti-inflammatory drugs (NSAID), even if short-term, may be associated to small intestinal complications, such as erosions, ulcers and chronic mucosal inflammation. Video capsule endoscopy allows for identification of such lesions in 20 to 55% of the patients who have taken nonselective NSAID for 2 to 4 weeks. The pathophysiology of NSAID-induced enteropathy is related to a reduced reparative potential of the mucosa and abnormalities of the microbial balance in the small intestine. In real world practice, NSAID enteropathy is commonly asymptomatic, and its manifestations, such as bleeding, perforation and ileus, are quite rare (about 0.3 episodes per 100 patient-years). The main manifestation of NSAID enteropathy is chronic iron deficient anemia. The use of rebamipide, sulfasalazine, mesalazine, and rifaximin has been discussed in the treatment of NSAID enteropathy, whereas its prevention implies preferential administration of coxibs, the use of rebamipide and probiotics.

NSAID Enteropathy: A Review of the Disease Entity and Its Distinction from Crohn’s Enteropathy

Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is an increasingly recognized entity. Patients of older age and those suffering from conditions such as arthritis requiring long term NSAIDs are thought to be at greater risk. Introduction of enteroscopic techniques has greatly improved understanding of NSAID-related small intestinal injury. Complementary high-resolution cross-sectional imaging techniques aid in initial evaluation and for exclusion of alternative etiology. Erosions, superficial ulcerations, and short segment strictures are the most commonly described findings. The diagnosis of the condition lies in obtaining relevant history in addition to a high degree of suspicion during investigation of anemia, obscure gastrointestinal bleeding, small bowel obstruction, and protein losing enteropathy. Herein, the authors present a review of pathogenesis and imaging findings of NSAID enteropathy with particular emphasis on distinction from Crohn’s enteropathy.

NSAID-induced enteropathy: the current state of the problem

The review analyzes the main etiological and pathogenetic mechanisms of the development of NSAID-enteropathy. Particular attention is paid to the role of intestinal microbiota in the manifestation and progression of NSAID-enteropathy. The special role of probiotics in the prevention and treatment of NSAIDs enteropathy is considered.