ORIGINAL ARTICLE Multidrug resistance gene deficient (mdr1a – ⁄ – ) mice have an altered caecal microbiota that precedes the onset of intestinal inflammation K. Nones 1 , B. Knoch 2,3 , Y.E.M. Dommels 1 , G. Paturi 1 , C. Butts 1 , W.C. McNabb 2 and N.C. Roy 2 1 Crop & Food Research, Palmerston North, New Zealand 2 Food, Metabolism & Microbiology, AgResearch Grasslands, Palmerston North, New Zealand 3 Institute of Food, Nutrition & Human Health, Massey University, Palmerston North, New Zealand Introduction The interaction between intestinal microbiota and host may play an important role in intestinal inflammation in humans and in mice (Mahida and Rolfe 2004). Frank et al. (2007) showed differences between the intestinal microbiota of patients with inflammatory bowel disease (IBD) and healthy individuals. It remains unclear, how- ever, whether the inflammatory responses in IBD are influenced by specific intestinal microbiota or whether tolerance to commensal microbiota in general is affected (O’Hara and Shanahan 2006; Frank et al. 2007). The genetically engineered mdr1a – ⁄ – mouse carries a disruption of multi-drug resistance gene (Schinkel et al. 1994) and spontaneously develops intestinal inflammation in spite of the presence of an intact immune system (Panwala et al. 1998). The mdr1a gene encodes for P-glycoprotein (also known as Abcb1 transporter), allelic Keywords Bacteroides, IBD, mdr1a – ⁄ – mice, microbiota. Correspondence Christine Butts, Crop & Food Research, Private Bag 11600, Palmerston North 4442, New Zealand. E-mail: buttsc@crop.cri.nz 2008 ⁄ 1789: received 18 October 2008, revised 21 December 2008 and accepted 26 December 2008 doi:10.1111/j.1365-2672.2009.04225.x Abstract Aim: To compare caecal microbiota from mdr1a – ⁄ – and wild type (FVB) mice to identify differences in the bacterial community that could influence the intestinal inflammation. Methods and Results: Caecal microbiota of mdr1a – ⁄ – and FVB mice were eval- uated at 12 and 25 weeks of age using denaturing gradient gel electrophoresis (DGGE) and quantitative real-time PCR. DGGE fingerprints of FVB and mdr1a – ⁄ – mice (with no intestinal inflammation) at 12 weeks revealed differ- ences in the presence of DNA fragments identified as Bacteroides fragilis, B. thetaiotaomicron, B. vulgatus and an uncultured alphaproteobacterium. Escherichia coli and Acinetobacter sp. were only identified in DGGE profiles of mdr1a – ⁄ – mice at 25 weeks (with severe intestinal inflammation), which also had a lower number of total bacteria in the caecum compared with FVB mice at same age. Conclusions: Differences found in the caecal microbiota of FVB and mdr1a – ⁄ – mice (12 weeks) suggest that the lack of Abcb1 transporters in intestinal cells due to the disruption of the mdr1a gene might lead to changes in the caecal microbiota. The altered microbiota along with the genetic defect could contri- bute to the development of intestinal inflammation in mdr1a – ⁄ – mice. Significance and Impact of the Study: Differences in caecal microbiota of mdr1a – ⁄ – and FVB mice (12 weeks) suggest genotype specific colonization. The results provide evidence that Abcb1 transporters may regulate host interactions with commensal bacteria. Future work is needed to identify the mechanisms involved in this possible cross-talk between the host intestinal cells and microbiota. Journal of Applied Microbiology ISSN 1364-5072 ª 2009 The Authors Journal compilation ª 2009 The Society for Applied Microbiology, Journal of Applied Microbiology 107 (2009) 557–566 557