Connective remodelling in the colonic neuromuscular compartment of patients with ulcerative colitis

Objectives. Chronic inflammatory conditions may progress towards tissue remodelling processes, which are often characterized by an enhanced collagen deposition. As far as inflammatory bowel diseases are concerned, consistent levels of fibrotic remodelling have been identified and investigated in Crohn’s disease, while scarce attention to such a tissue rearrangement has been paid to ulcerative colitis (UC). The present study evaluated the distribution of collagen and elastic fibers in the colonic neuromuscular compartment of patients with UC. Methods. Full-thickness left colonic samples were obtained from 10 patients with established, severe and pharmacologically unresponsive UC, who underwent bowel resection. The colonic neuromuscular compartment was evaluated by routine histology, histochemistry and immunohistochemistry in paraffin cross-sections. The distribution of collagen and elastic fibers was evaluated by both histochemical (Van Gieson, orcein, Verroheff staining) and immunohistochemical (anti-collagen I and III, anti-elastin) assays. For comparison, the same evaluations were performed in normal colonic control samples from 10 subjects, who underwent surgery for uncomplicated colon cancer. Results. Histochemical and immunohistochemical analysis of the inflamed colon showed a significant increase in collagen fibers and a decrease in elastin content within the neuromuscular compartment, as compared with normal controls. In particular, increments of collagen deposition (mainly collagen type III) were found at level of the outer layers of longitudinal muscle (serosal side; arranged as bunches of fibers intermingled with bundles of smooth muscle cells), within the circular muscle layer (arranged as tangles of fibers along the longitudinal axis of smooth muscle cells), and in perivascular connective tissue. By contrast, elastic fibers were significantly and homogeneously reduced throughout the whole neuromuscular compartment, with particular regard for the myenteric ridge. Conclusions. The present findings indicate that a significant degree of fibrotic remodelling occurs in the neuromuscular compartment of the inflamed colonic wall in patients with UC. This rearrangement of the connective tissue, taken together with the known alterations affecting the myenteric ganglionic cells and interstitial cells of Cajal, likely contributes to the development of enteric dysmotility, leading to serious digestive symptoms in patients with UC.