Neuroimmunomodulation in the Gut: Focus on Inflammatory Bowel Disease.

Intestinal immunity is finely regulated by several concomitant and overlapping mechanisms, in order to efficiently sense external stimuli and mount an adequate response of either tolerance or defense. In this context, a complex interplay between immune and nonimmune cells is responsible for the maintenance of normal homeostasis. However, in certain conditions, the disruption of such an intricate network may result in intestinal inflammation, including inflammatory bowel disease (IBD). IBD is believed to result from a combination of genetic and environmental factors acting in concert with an inappropriate immune response, which in turn interacts with nonimmune cells, including nervous system components. Currently, evidence shows that the interaction between the immune and the nervous system is bidirectional and plays a critical role in the regulation of intestinal inflammation. Recently, the maintenance of intestinal homeostasis has been shown to be under the reciprocal control of the microbiota by immune mechanisms, whereas intestinal microorganisms can modulate mucosal immunity. Therefore, in addition to presenting the mechanisms underlying the interaction between immune and nervous systems in the gut, here we discuss the role of the microbiota also in the regulation of neuroimmune crosstalk involved in intestinal homeostasis and inflammation, with potential implications to IBD pathogenesis.

Use of butyrate or glutamine in enema solution reduces inflammation and fibrosis in experimental diversion colitis.

AIM: To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis. METHODS: Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing glutamine, butyrate, or saline. Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure. Follow-up colonoscopy was performed every 4 wk for 12 wk. The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1ß, tumor necrosis factor-alpha, and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay. RESULTS: Colonoscopies of the diverted segment showed mucosa with hyperemia, increased number of vessels, bleeding and mucus discharge. Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic (P < 0.02) and histological scores (P < 0.01) and restored the densities of collagen fibers in tissue (P = 0.015; P = 0.001), the number of goblet cells (P = 0.021; P = 0.029), and the rate of apoptosis within the epithelium (P = 0.043; P = 0.011) to normal values. The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine. CONCLUSION: The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.

Analysis of mutations in TP53, APC, K-ras, and DCC genes in the non-dysplastic mucosa of patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Patients with ulcerative colitis (UC) and Crohn's disease (CD) have a high risk for colorectal cancer (CRC). To understand the molecular basis of colitis-associated CRC, we analyzed alterations in TP53, APC, K-ras, and DCC genes in the non-dysplastic UC and CD colon. MATERIALS AND METHODS: Endoscopic biopsies were collected from six predefined colon sites of 35 UC and 12 CD patients for DNA extraction and genetic analysis. RESULTS: A mutation was found in codon 1141 of the APC gene of two CD patients, being somatic in one and germinative in the other. The mutation seen in both patients was a base exchange of thymine for cytosine, resulting in an exchange of leucine for serine. We did not detect any mutations in the other samples analyzed. CONCLUSIONS: Mutations in APC gene may occur in the non-dysplastic CD mucosa of patients with disease for more than 10 years. The follow-up of these patients will show the likelihood of mutant APC progressing to CRC in CD. Further analysis will be required for evaluating the impact of these findings in the context of cancer surveillance in inflammatory bowel disease.