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Applied and Environmental Microbiology, October 2006, p. 6707-6715, Vol. 72, No. 10
0099-2240/06/$08.00+0     doi:10.1128/AEM.00378-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Culture-Independent Analysis of Indomethacin-Induced Alterations in the Rat Gastrointestinal Microbiota

Andrew B. Dalby,1 Daniel N. Frank,1 Allison L. St. Amand,1 Alison M. Bendele,2 and Norman R. Pace1*

Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309-0347,1 Bolder BioPATH, Inc., University of Colorado, Boulder, Colorado 80309-03472

Received 15 February 2006/ Accepted 6 August 2006

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for a variety of inflammatory conditions; however, the benefits of this class of drugs are accompanied by deleterious side effects, most commonly gastric irritation and ulceration. NSAID-induced ulceration is thought to be exacerbated by intestinal microbiota, but previous studies have not identified specific microbes that contribute to these adverse effects. In this study, we conducted a culture-independent analysis of ~1,400 bacterial small-subunit rRNA genes associated with the small intestines and mesenteric lymph nodes of rats treated with the NSAID indomethacin. This is the first molecular analysis of the microbiota of the rat small intestine. A comparison of clone libraries and species-specific quantitative PCR results from rats treated with indomethacin and untreated rats revealed that organisms closely related to Enterococcus faecalis were heavily enriched in the small intestine and mesenteric lymph nodes of the treated rats. These data suggest that treatment of NSAID-induced ulceration may be facilitated by addressing the microbiological imbalances.

* Corresponding author. Mailing address: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347. Phone: (303) 735-1864. Fax: (303) 492-7744. E-mail: nrpace{at}colorado.edu.

Applied and Environmental Microbiology, October 2006, p. 6707-6715, Vol. 72, No. 10
0099-2240/06/$08.00+0     doi:10.1128/AEM.00378-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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