Background: Specific pathogen-free (SPF), but not germfree (GF), interleukin (IL)-2-deficient (IL-2−/−) mice develop inflammatory bowel disease (IBD) at 10 to 15 weeks of age. Gnotobiotic IL-2−/− mice monocolonized with E. coli mpk develop IBD at 25 to 33 weeks of age but not B. vulgatus mpk, E. coli Nissle 1917, or mice cocolonized with both E. coli mpk and B. vulgatus. Methods: To determine genes regulated by these commensal bacteria, host gene expression in the colon of 8-week-old IL-2−/− mice was compared by using microarrays and semiquantitative reverse-transcription polymerase chain reaction. Colonization with E. coli mpk/B. vulgatus or SPF microbiota altered the gene expression profile more profoundly than monocolonization with either B. vulgatus, E. coli mpk or E. coli Nissle indicating that the complexity of the gene expression pattern is influenced by the diversity of the microbiota. Results: A small but distinct group of genes could be defined which might be associated with colitis development. Thus, 8 week old E. coli mpk IL-2−/− mice rone to colitis compared to E. coli Nissle, B. vulgatus and E. coli mpk/B. vulgatus IL-2−/− mice displayed a lower expression of the anti-inflammatory RegIII family genes such as RegIIIγ and pancreatitis associated protein (PAP) and peroxisome proliferator-activated receptor-γ regulated genes such as adipsin and adiponectin. Conclusion: The increased expression of these genes in B. vulgatus colonized mice might be associated with prevention of E. coli mpk triggered colitis in E. coli mpkM/B. vulgatus IL-2−/− mice.