Altered enteric microbiota ecology in interleukin 10-deficient mice during development and progression of intestinal inflammation

Nitsan Maharshak, Christopher D. Packey, Melissa Ellermann, Sayeed Manick, Jennica P. Siddle, Eun Young Huh, Scott Plevy, R. Balfour Sartor, Ian M. Carroll

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Inflammatory bowel diseases (IBD) result from dysregulated immune responses toward microbial and perhaps other luminal antigens in a genetically susceptible host, and are associated with altered composition and diversity of the intestinal microbiota. The interleukin 10 -deficient (IL-10-/-) mouse has been widely used to model human IBD; however the specific alterations that occur in the intestinal microbiota of this mouse model during the onset of colonic inflammation have not yet been defined. The aim of our study was to define the changes in diversity and composition that occur in the intestinal microbiota of IL-10-/- mice during the onset and progression of colonic inflammation. We used high throughput sequencing of the 16s rRNA gene to characterize the diversity and composition of formerly germ-free, wild-type and IL-10-/- mice associated with the same intestinal microbiota over time. Following two weeks of colonization with a specific pathogen-free (spF) microbiota we observed a significant increase in the diversity and richness of the intestinal microbiota of wild-type mice. In contrast, a progressive decrease in diversity and richness was observed at three and four weeks in IL-10-/- mice. This decrease in diversity and richness was mirrored by an increase in proteobacteria and Escherichia coli i n I L - 1 0 -/- mice. An increase in E. coli was also observed in conventionally raised IL-10-/- mice at the point of colonic inflammation. Our data report the sequential changes in diversity and composition of the intestinal microbiota in an immune-mediated mouse model that may help provide insights into the primary vs. secondary role of dysbiosis in human IBD patients.

Original languageEnglish
Pages (from-to)316-324
Number of pages9
JournalGut Microbes
Volume4
Issue number4
DOIs
StatePublished - Jul 2013
Externally publishedYes

Funding

FundersFunder number
NIH T32 DK07737 institutinal researchT32 DK07737
NIH T35 DK007386 short-termK01 DK 092330, R01 DK 53347, T35 DK007386
National Gnotobiotic Rodent Resource Center
UNC-CH university research council
USPHS P40 OD010995P30 DK 34987-10, P40 OD010995
National Institute of Diabetes and Digestive and Kidney DiseasesP30DK034987
Crohn's and Colitis Foundation of America
Center for Outcomes Research and Evaluation, Yale School of MedicineP30 DK 34987
University of North Carolina at Chapel Hill
University Research Council, DePaul University

    Keywords

    • Inflammatory bowel diseases
    • Interleukin 10-deficient mouse
    • Intestinal microbiota

    Fingerprint

    Dive into the research topics of 'Altered enteric microbiota ecology in interleukin 10-deficient mice during development and progression of intestinal inflammation'. Together they form a unique fingerprint.

    Cite this