Antibiotics with a selective aerobic or anaerobic spectrum have different therapeutic activities in various regions of the colon in interleukin 10 gene deficient mice

Abstract

Background and aims: Multiple rodent models implicate resident intestinal bacteria in the pathogenesis of chronic immune mediated intestinal inflammation. Specific pathogen free (SPF) interleukin 10 gene deficient (IL-10 2/2 ) mice develop colitis, which does not occur in the germ free (GF) state. We investigated whether broad or narrow spectrum antibiotics affect onset and progression of disease in various regions of IL-10 2/2 mice. Methods: Metronidazole, ciprofloxacin, vancomycin-imipenem (50 mg/kg/day), or water (control) was administered orally before (prevention) or two weeks after (treatment) colonisation of GF IL-10 2/2 mice with SPF bacteria. After four weeks, colonic histology scores and cytokine production by colonic explants were determined. Caecal and colonic contents were collected for quantitative bacterial analysis. Results: In the prevention study, all antibiotics decreased inflammation in the caecum and colon. However, in the treatment study, ciprofloxacin and vancomycin-imipenem decreased caecal inflammation, and reduced Escherichia coli and Enterococcus faecalis concentrations, whereas only vancomycin-imipenem lowered direct microscopic bacterial counts. In contrast, metronidazole and vancomycin-imipenem reduced colonic injury and eliminated anaerobic bacteria, including Bacteroides spp. Conclusions: Both narrow and broad spectrum antibiotics can prevent disease but treatment of established colitis is more selective. Ciprofloxacin is most effective in the treatment of caecal inflammation, metronidazole preferentially treats the colon, whereas vancomycin-imipenem definitively treats both regions. These results suggest that subsets of aerobic or anaerobic bacteria show regional differences in their capacity to mediate experimental colitis in IL-10 2/2 mice.

A breakthrough in probiotics: Clostridium butyricum regulates gut homeostasis and anti-inflammatory response in inflammatory bowel disease

“…Furthermore, IL-10-deficient mice developed inflammation restricted to the colon, suggesting that the resident microbiota plays a role in the development of spontaneous colitis [50]. Consistent with this observation, antibiotic therapy can prevent the development of colitis in IL-10 knockout mice [121,122]. In addition, germ-free IL-10 knockout mice developed colitis after they were colonized with Enterococcus faecalis [123].…”

Abnormally Differentiated Subsets of Intestinal Macrophage Play a Key Role in Th1-Dominant Chronic Colitis through Excess Production of IL-12 and IL-23 in Response to Bacteria

“…Ϫ/Ϫ mice show Th1 polarized immunity upon exposure to bacteria, whereas germfree conditions prevent development of intestinal inflammation (15), and treatment with antibiotics attenuates intestinal inflammation (16,17). These facts suggest that enteric bacteria play essential roles in onset and development of colitis in IL-10 Ϫ/Ϫ mice, similar to human IBDs.…”

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).…”