Circumstances where the infection cannot be cleared or tolerance to the commensal flora is lost, could lead to a chronic inflammatory state. The interaction between the host and the microbiota of the Paclitaxel structure gastrointestinal tract, therefore, play important roles in both health and disease. The epithelial cells of the colon are responsible for development of the physical barrier that separates the host from coming into direct contact with the commensal flora. Mucous producing goblet cells are more abundant in the bacteria-dense colon than in the small intestine, where bacteria are present at orders of magnitude lower concentrations. There is some evidence that mucous thickness and the continuity of the mucous barrier correlates with disease severity of ulcerative colitis [30], [31].

DSS-induced colitis is often used as a model of epithelial barrier disruption to test clinical compounds and explore the molecular mechanisms underlying colonic inflammation in the preclinical setting. DSS treatment results in progressive loss of the mucous layer and direct contact of the commensal flora of the gastrointestinal tract with the host resulting in a robust inflammatory response [22]. In this study we considered DSS damage of the colonic mucous layer as a mechanistic model of environmental factors (eg. drugs, smoking, alcohol, allergens and pathogens) that can potentially disrupt the epithelial barrier of the colon bringing the commensal flora and the host in proximity to each other.

The data presented demonstrate that initiating contact between the host and commensal bacteria results in a progressive development of the host immune response resulting in clearance of the bacterial load over time. Clearance of bacteria occurs with a significant impact on the community structure of the tissue-associated microflora as demonstrated by statistical examination of the composition of the commensal bacteria before and after damage (Table 1). Host genetics – as determined in our studies by the comparison of WT mice with Nod2 littermates �Csignificantly regulates the accumulation of bacteria following DSS damage in Nod2 KO animals (Figure 4, Figure S4) playing a significant role a role in reestablishing host/bacterial homeostasis. Nod2 does not only regulate bacterial clearance; as demonstrated GSK-3 by our study and others its presence or absence has a significant impact on the community structure of the tissue-associated commensal community structure [28]. Taken together, the data presented in this study experimentally demonstrate the contribution of genetic and environmental factors in the ecological succession of the commensal flora. In the womb, mammals reside in a sterile environment acquiring their flora upon birth.