title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Otani
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanigawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.forename: Sunao
authors.initials: S
authors.lastname: Shimada
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nadatani
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Nagami
authors.forename: Fumio
authors.initials: F
authors.lastname: Tanaka
authors.forename: Noriko
authors.initials: N
authors.lastname: Kamata
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamagami
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Shiba
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tominaga
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007410:Intestinal Diseases / Q000139:chemically induced / Q000382:microbiology* / Q000517:prevention & control; D007421:Intestine, Small / Q000187:drug effects / Q000382:microbiology; D019936:Probiotics / Q000627:therapeutic use; D015363:Quinolones / Q000627:therapeutic use; D014456:Ulcer / Q000139:chemically induced / Q000382:microbiology / Q000517:prevention & control
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D015363:Quinolones; C052785:rebamipide; D000409:Alanine