title: Indomethacin injury to the rat small intestine is dependent upon biliary secretion and is associated with overgrowth of enterococci.
abstract: NSAIDuse is limited due to the drugs' toxicity to the gastrointestinal mucosa, an action incompletely understood. Lower gut injury induced byNSAIDs 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 orINDO, 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, onlySO/INDOrats experienced a significant 10- to 30-fold increase in fecal Hb and reduction in Hct, indicating thatBDLattenuatedINDO-induced intestinal injury/bleeding. Ileal enterococcal colony-forming units were significantly increased (500- to 1000-fold) inSO/INDOrats. Of all groups, only theSO/INDOrats demonstrated gut injury, and this was associated with enterococcal overgrowth of the gut and dissemination to the liver. We also demonstrated thatINDO-induced intestinal injury andE. faecalisovergrowth was independent of the route of administration of the drug, as similar findings were observed in rats orally dosed with theNSAID Bile secretion plays an important role inINDO-induced gut injury and appears to support enterococcal overgrowth of the intestine.NSAID-induced enterococcalSBOmay be involved either as a compensatory response to gut injury or with the pathogenic process itself and the subsequent development of sepsis.
authors.affiliation: Departments of Integrative Biology & Pharmacology, Microbiology and Molecular Genetics, and Internal Medicine-Infectious Diseases, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Mayo
authors.affiliation: Departments of Integrative Biology & Pharmacology, Microbiology and Molecular Genetics, and Internal Medicine-Infectious Diseases, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Ye K
authors.initials: YK
authors.lastname: Song
authors.affiliation: Departments of Integrative Biology & Pharmacology, Microbiology and Molecular Genetics, and Internal Medicine-Infectious Diseases, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Cruz
authors.affiliation: Departments of Integrative Biology & Pharmacology, Microbiology and Molecular Genetics, and Internal Medicine-Infectious Diseases, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Tri M
authors.initials: TM
authors.lastname: Phan
authors.affiliation: Departments of Integrative Biology & Pharmacology, Microbiology and Molecular Genetics, and Internal Medicine-Infectious Diseases, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Kavindra V
authors.initials: KV
authors.lastname: Singh
authors.affiliation: Departments of Integrative Biology & Pharmacology, Microbiology and Molecular Genetics, and Internal Medicine-Infectious Diseases, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Garsin
authors.affiliation: Departments of Integrative Biology & Pharmacology, Microbiology and Molecular Genetics, and Internal Medicine-Infectious Diseases, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Murray
authors.affiliation: Departments of Integrative Biology & Pharmacology, Microbiology and Molecular Genetics, and Internal Medicine-Infectious Diseases, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Dial
authors.affiliation: Departments of Integrative Biology & Pharmacology, Microbiology and Molecular Genetics, and Internal Medicine-Infectious Diseases, The University of Texas Health Science Center at Houston, Houston, Texas Lenard.M.Lichtenberger@uth.tmc.edu.
authors.forename: Lenard M
authors.initials: LM
authors.lastname: Lichtenberger
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018988:Bacterial Translocation; D001646:Bile / Q000378:metabolism*; D001652:Bile Ducts / Q000378:metabolism* / Q000601:surgery; D004195:Disease Models, Animal; D013293:Enterococcus faecalis / Q000254:growth & development* / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D006454:Hemoglobins / Q000378:metabolism; D007077:Ileal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D007082:Ileum / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D007213:Indomethacin; D008026:Ligation; D008099:Liver / Q000382:microbiology; D008297:Male; D017207:Rats, Sprague-Dawley
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006454:Hemoglobins; D007213:Indomethacin
keywords: Bile acid; Enterococcus faecalis; non‐steroidal anti‐inflammatory drugs