Different Subsets of Enteric Bacteria Induce and Perpetuate Experimental Colitis in Rats and Mice

Abstract

Resident bacteria are incriminated in the pathogenesis of experimental colitis and inflammatory bowel diseases. We investigated the relative roles of various enteric bacteria populations in the induction and perpetuation of experimental colitis. HLA-B27 transgenic rats received antibiotics (ciprofloxacin, metronidazole, or vancomycin-imipenem) in drinking water or water alone in either prevention or treatment protocols. Mice were treated similarly with metronidazole or vancomycin-imipenem before or after receiving 5% dextran sodium sulfate (DSS). Germfree transgenic rats were colonized with specific-pathogen-free enteric bacteria grown overnight either in anaerobic or aerobic atmospheres. Nontransgenic rats colonized with anaerobic bacteria served as negative controls. Although preventive metronidazole significantly attenuated colitis in transgenic rats and DSS-treated mice, it had no therapeutic benefit once colitis was established. Ciprofloxacin also partially prevented but did not treat colitis in B27 transgenic rats. In both animal models vancomycinimipenem most effectively prevented and treated colitis. Germfree transgenic rats reconstituted with enteric bacteria grown under anaerobic conditions had more aggressive colitis than those associated with aerobic bacteria. These results suggest that a subset of resident luminal bacteria induces colitis, but that a complex interaction of commensal aerobic and anaerobic bacteria provides the constant antigenic drive for chronic immune-mediated colonic inflammation.Rapidly growing evidence supports the influence of normal enteric bacteria on the pathogenic process of intestinal inflammation and extraintestinal manifestations in experimental colitis and human inflammatory bowel diseases (IBD) (40-43). Both spontaneous and induced inflammation in multiple widely diverse rodent models have been associated with commensal luminal bacteria (1, 11-13, 16, 22, 31, 44, 45, 52, 54). The influence of resident bacteria on the induction and perpetuation of spontaneous colitis and gastritis has been thoroughly studied in HLA-B27/␤ 2 -microglobulin transgenic (B27 TG) rats. Colitis, gastritis, and joint inflammation fail to develop in B27 TG rats raised under germfree (sterile) conditions (36, 49). Moreover, when transferred into a specific-pathogenfree (SPF) environment, B27 TG rats universally develop immune-mediated colitis and gastritis within 1 month of bacterial colonization (36).However, not all luminal bacteria have equal abilities to cause inflammation. Antibiotics with narrow specificities, such as metronidazole, which is selectively active against anaerobic bacteria, are effective in Crohn's colitis and ileocolitis (47) and also attenuate chronic experimental intestinal inflammation induced by indomethacin or carageenan in rats and guinea pigs, respectively (32, 54). In addition, overgrowth of predominantly anaerobic bacteria in bypassed small intestinal segments can lead to systemic inflammation. A jejunal self-filling blind loop induces hepatobiliary inflammation rese...

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

“…Finally, over 30 animal models have been described that mimic human inflammatory bowel disease (22). In general, these animals do not develop intestinal inflammation in the absence of commensal bacteria (23)(24)(25)(26)(27)(28). These data support a role for bacterial epithelial interactions in the development or perpetuation of intestinal inflammation.…”

Regulation of dextran sodium sulfate induced colitis by leukocyte beta 2 integrins

“…54,55 Moreover, it has been reported that the severity of DSS colitis is influenced by enteric bacterial; therefore, it could be that genetic loss of CD11b is permissive for bacterial translocation from the colon thereby enhancing disease. 56,57 Blood and mesenteric lymph node cultures from all of the genetic variants in this study were not different from one another, suggesting that bacterial burden is not a mitigating factor for enhanced disease activity in CD11b null mice.…”

Gram-Negative Bacteria Aggravate Murine Small Intestinal Th1-Type Immunopathology following Oral Infection with Toxoplasma gondii

“…detected in experimental colitis (61,62) and in patients with IBD (13). Furthermore, the colitogenic potential of both bacterial groups was determined earlier (18,19,21,63) and the contributions of Gram-negative bacteria to the severity of intestinal inflammation were supported by successful antibiotic treatment of experimental colitis and in human IBD (22,64,65), as well as in GvHD (8).…”