The nematode Trichuris muris has been shown to interact with specific enteric bacteria, but its effects on the composition of its host's microbial community are not fully understood. We hypothesized that Trichuris muris-infected mice would have altered colon microbiota as compared with uninfected mice. Colon histopathology and microbial community structure and composition were examined in mouse models of colitis (C3BirTLR4-/- IL10-/- and C3H/HeJ TLR4-/- IL10+/+ mice) with and without T. muris infection, in uninfected C3BirIL10-/- mice with and without spontaneous colitis, and in normal C3H/ HeJ mice. T. muris-infected mice developed colon lesions that were more severe than those seen in IL10-deficient mice. Ap- proximately 80% of infected IL10-/- mice had colon neutrophilic exudates, and some had extraintestinal worms and bacteria. The composition and structure of proximal colon microbiota were assessed by using terminal restriction fragment length polymorphism analysis targeting the bacterial 16S rRNA gene. Colon microbiota in C3BirIL10-/- and C3H/HeJ mice differed both qualitatively and quantitatively. Trichuris infection significantly altered the relative abundance of individual operational taxonomic units [OTU] but not the composition (presence or absence of OTU) of colon microbiota in the 2 mouse genotypes. When C3BirIL10-/- and C3H/HeJ mouse OTU were considered separately, Trichuris was found to affect the microbiota of C3BirIL10-/- mice but not of C3H/HeJ mice. Even though 34 of the 75 (45%) C3BirIL10-/- mice had spontaneous colitis, neither qualitative nor quantitative differences were detected in microbiota between colitic or noncolitic C3BirIL10-/- mice or noncolitic C3H/HeJ mice. Therefore, Trichuris-infected mice developed distinct microbial communities that were influenced by host background genes; these alterations cannot be attributed solely to colonic inflammation.