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PLoS One. 2012;7(1):e30273. doi: 10.1371/journal.pone.0030273. Epub 2012 Jan 17.

Host genetics and environmental factors regulate ecological succession of the mouse colon tissue-associated microbiota.

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  • 1Novartis Institutes for Biomedical Research, Gastrointestinal Disease Area, Horsham, West Sussex, United Kingdom.



The integration of host genetics, environmental triggers and the microbiota is a recognised factor in the pathogenesis of barrier function diseases such as IBD. In order to determine how these factors interact to regulate the host immune response and ecological succession of the colon tissue-associated microbiota, we investigated the temporal interaction between the microbiota and the host following disruption of the colonic epithelial barrier.


Oral administration of DSS was applied as a mechanistic model of environmental damage of the colon and the resulting inflammation characterized for various parameters over time in WT and Nod2 KO mice.


In WT mice, DSS damage exposed the host to the commensal flora and led to a migration of the tissue-associated bacteria from the epithelium to mucosal and submucosal layers correlating with changes in proinflammatory cytokine profiles and a progressive transition from acute to chronic inflammation of the colon. Tissue-associated bacteria levels peaked at day 21 post-DSS and declined thereafter, correlating with recruitment of innate immune cells and development of the adaptive immune response. Histological parameters, immune cell infiltration and cytokine biomarkers of inflammation were indistinguishable between Nod2 and WT littermates following DSS, however, Nod2 KO mice demonstrated significantly higher tissue-associated bacterial levels in the colon. DSS damage and Nod2 genotype independently regulated the community structure of the colon microbiota.


The results of these experiments demonstrate the integration of environmental and genetic factors in the ecological succession of the commensal flora in mammalian tissue. The association of Nod2 genotype (and other host polymorphisms) and environmental factors likely combine to influence the ecological succession of the tissue-associated microflora accounting in part for their association with the pathogenesis of inflammatory bowel diseases.

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