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

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.

Uric acid ameliorates indomethacin‐induced enteropathy in mice through its antioxidant activity

“…As bile and intestinal flora play important roles in the pathogenesis of indomethacin‐induced enteropathy, further analysis will be needed to show the effect of administration of uric acid or IMP with KOX on enterohepatic circulation and gut microbiota. In addition, the incidence of taking indomethacin recently seems to have become less frequent for humans.…”

Efficacy of Ceftaroline against Methicillin-Susceptible Staphylococcus aureus Exhibiting the Cefazolin High-Inoculum Effect in a Rat Model of Endocarditis

“…The numbers of bacterial CFU per gram were log transformed to negate the effect of large positive skewing of recovery values prior to performing unpaired t tests to obtain P values (21,56,(61)(62)(63)(64). Cultures yielding no growth were scored as sterile and were assigned a value of 1 CFU for statistical analysis or to obtain geometric means of CFU per gram of vegetation.…”

“…Cultures yielding no growth were scored as sterile and were assigned a value of 1 CFU for statistical analysis or to obtain geometric means of CFU per gram of vegetation. In animals that had only 1 colony recovered from the entire undiluted tissue homogenate, this value was converted to the number per gram of tissue (as was done with other recovered CFU) to determine the minimum detection limit (MDL) CFU per gram (21,56,(61)(62)(63)(64). Data and graphs were generated using Prism for Windows (version 4.00; GraphPad Software).…”

The gut microbiome and the mechanism of surgical infection

“…This may even include the more common non‐steroidal anti‐inflammatory drug (NSAID)‐mediated ulcers that are rapidly becoming the most common cause of ulcer disease. For example, mice chronically fed NSAIDs will develop spontaneous intestinal ulcers and perforations, whereas mice treated with antibiotics or raised in germ‐free conditions are protected against these NSAID‐induced effects. The clinical context of these experimental observations may be significant.…”