title: NSAID enteropathy and bacteria: a complicated relationship.
abstract: The clinical significance of small intestinal damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs) remains under-appreciated. It occurs with greater frequency than the damage caused by these drugs in the upper gastrointestinal tract, but is much more difficult to diagnose and treat. Although the pathogenesis of NSAID enteropathy remains incompletely understood, it is clear that bacteria, bile, and the enterohepatic circulation of NSAIDs are all important factors. However, they are also interrelated with one another. Bacterial enzymes can affect the cytotoxicity of bile and are essential for enterohepatic circulation of NSAIDs. Gram-negative bacteria appear to be particularly important in the pathogenesis of NSAID enteropathy, possibly through release of endotoxin. Inhibitors of gastric acid secretion significantly aggravate NSAID enteropathy, and this effect is due to significant changes in the intestinal microbiome. Treatment with antibiotics can, in some circumstances, reduce the severity of NSAID enteropathy, but published results are inconsistent. Specific antibiotic-induced changes in the microbiota have not been causally linked to prevention of intestinal damage. Treatment with probiotics, particularly Bifidobacterium, Lactobacillus, and Faecalibacteriaum prausnitzii, has shown promising effects in animal models. Our studies suggest that these beneficial effects are due to colonization by the bacteria, rather than to products released by the bacteria.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Canada.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Syer
authors.forename: Rory W
authors.initials: RW
authors.lastname: Blackler
authors.forename: Rebeca
authors.initials: R
authors.lastname: Martin
authors.forename: Giada
authors.initials: G
authors.lastname: de Palma
authors.forename: Laura
authors.initials: L
authors.lastname: Rossi
authors.forename: Elena
authors.initials: E
authors.lastname: Verdu
authors.forename: Premek
authors.initials: P
authors.lastname: Bercik
authors.forename: Michael G
authors.initials: MG
authors.lastname: Surette
authors.forename: Anne
authors.initials: A
authors.lastname: Aucouturier
authors.forename: Philippe
authors.initials: P
authors.lastname: Langella
authors.forename: John L
authors.initials: JL
authors.lastname: Wallace
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D054884:Host-Pathogen Interactions; D006801:Humans; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000382:microbiology / Q000517:prevention & control; D007421:Intestine, Small / Q000187:drug effects* / Q000382:microbiology*; D064307:Microbiota / Q000502:physiology*; D019936:Probiotics / Q000627:therapeutic use; D014456:Ulcer / Q000139:chemically induced / Q000382:microbiology / Q000517:prevention & control
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal