Indomethacin injury to the rat small intestine is dependent upon biliary secretion and is associated with overgrowth of enterococci

Sara A. Mayo, Ye K. Song, Melissa R. Cruz, Tri M. Phan, Kavindra V. Singh, Danielle A. Garsin, Barbara E. Murray, Elizabeth J. Dial, Lenard M. Lichtenberger

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

NSAID use is limited due to the drugs' toxicity to the gastrointestinal mucosa, an action incompletely understood. Lower gut injury induced by NSAIDs is dependent on bile secretion and is reported to increase the growth of a number of bacterial species, including an enterococcal species, Enterococcus faecalis. This study examined the relationships between indomethacin (INDO)-induced intestinal injury/bleeding, small bowel overgrowth (SBO) and dissemination of enterococci, and the contribution of bile secretion to these pathological responses. Rats received either a sham operation (SO) or bile duct ligation (BDL) prior to administration of two daily subcutaneous doses of saline or INDO, and 24 h later, biopsies of ileum and liver were collected for plating on selective bacterial media. Fecal hemoglobin (Hb) and blood hematocrit (Hct) were measured to assess intestinal bleeding. Of the four treatment groups, only SO/INDO rats experienced a significant 10- to 30-fold increase in fecal Hb and reduction in Hct, indicating that BDL attenuated INDO-induced intestinal injury/bleeding. Ileal enterococcal colony-forming units were significantly increased (500- to 1000-fold) in SO/INDO rats. Of all groups, only the SO/INDO rats demonstrated gut injury, and this was associated with enterococcal overgrowth of the gut and dissemination to the liver. We also demonstrated that INDO-induced intestinal injury and E. faecalis overgrowth was independent of the route of administration of the drug, as similar findings were observed in rats orally dosed with the NSAID. Bile secretion plays an important role in INDO-induced gut injury and appears to support enterococcal overgrowth of the intestine. NSAID-induced enterococcal SBO may be involved either as a compensatory response to gut injury or with the pathogenic process itself and the subsequent development of sepsis.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalPhysiological reports
Volume4
Issue number6
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Keywords

  • Bile acid
  • Enterococcus faecalis
  • Non-steroidal anti-inflammatory drugs

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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