colon cancer, colorectal carcinoma, interstitial tissue, large bowel, pathology

Long lasting chronic inflammation induces progressive fibrosis of the involved tissues. Chronic inflammation, a leading factor in many pathological processes, can address cancer establishment and evolution. Local changes of immune activation inside a tissue, if maintained and supported by the environment, can induce structural remodeling. Reciprocally, collagen accumulation can affect the local immunity. We have shown that the colonization of germ-free (GF) mice colon by conventional mice (CV) intestinal microflora quickly modifies the local and systemic immunity. Contemporarily, it induces a fast remodeling of the collagen scaffold in the intestinal mucosa. Using a rat model of chronic colitis (dextran sodium sulphate — DSS — induced colitis) and of carcinogenesis (using azoxymethane — AOM - carcinogen for the colon) we have shown that, in both models, inflammation activates remodeling of the collagen scaffold organization even when the mucosa appears recovered from the acute induction. Multi-photon confocal microscopy of CV and GF animal mucosa resulted with higher complexity in structure in the CV rats (with microbiome). The immunological data suggest that the response to the microbiota presence elicit effective homeostatic regulation in the healthy CV rats, to avoiding inflammation and maintaining cytokine levels near the spontaneous production found in the GF animals. These conditions establish what we define as "inflammatory threshold" of the mucosa, allowing a range of tolerance to the continuous immune activation. The results also indicated that the collagen scaffold adapts to the immune microenvironment conditions, and quickly it can be altered if the immune threshold is overcome.