Varying cecal bacterial loads influences colitis and gastritis in HLA-B27 transgenic rats

Background & Aims: Recent data support an important role of resident luminal bacteria in experimental colitis. We determined how altered cecal bacterial loads influence colitis and gastritis. Methods: A cecal self-filling blind loop (SFBL) was created or the cecum was excluded from the fecal stream in specific pathogen-free HLA-B27 transgenic (TG) rats with early colitis and in nontransgenic (nonTG) littermates; controls underwent sham operation (SHAM). Luminal bacterial concentrations were determined by culture and counting chamber. Results: TG rats with SFBL had more severe cecal inflammation and leukocytosis than TG SHAM controls. TG excluded rats with low cecal bacterial loads had no cecal inflammation and less colitis and gastritis than SHAM controls, despite having normal distal colonic and gastric bacterial concentrations. Metronidazole attenuated cecal inflammation and eliminated Bacteroides in SFBL TG rats. NonTG SFBL rats had mild cecal inflammation and no gastritis and colitis. The ratio of total anaerobic to aerobic bacteria was 1000-fold greater in SFBL than in SHAM rats, with a 10,000-fold increased ratio of Bacteroides spp. to aerobes. Conclusions: The luminal bacterial load and composition determines the activity of cecal inflammation in genetically susceptible hosts. Lowering cecal bacterial concentrations can diminish inflammation in remote organs.