Abstract
BackgroundGut bacteria trigger colitis in animal models and are suspected to aggravate inflammatory bowel diseases. We have recently reported that Escherichia coli accumulates in murine ileitis and exacerbates small intestinal inflammation via Toll-like receptor (TLR) signaling.Methodology and Principal FindingsBecause knowledge on shifts in the intestinal microflora during colitis is limited, we performed a global survey of the colon flora of C57BL/10 wild-type (wt), TLR2-/-, TLR4-/-, and TLR2/4-/- mice treated for seven days with 3.5% dextrane-sulfate-sodium (DSS). As compared to wt animals, TLR2-/-, TLR4-/-, and TLR2/4-/- mice displayed reduced macroscopic signs of acute colitis and the amelioration of inflammation was associated with reduced IFN-gamma levels in mesenteric lymph nodes, lower amounts of neutrophils, and less FOXP3-positive T-cells in the colon in situ. During acute colitis E. coli increased in wt and TLR-deficient mice (P<0.05), but the final numbers reached were significantly lower in TLR2-/-, TLR4-/- and TLR2/4-/- animals, as compared to wt controls (P<0.01). Concentrations of Bacteroides/ Prevotella spp., and enterococci did not increase during colitis, but their numbers were significantly reduced in the colon of DSS-treated TLR2/4-/- animals (P<0.01). Numbers of lactobacilli and clostridia remained unaffected by colitis, irrespective of the TLR-genotype of mice. Culture-independent molecular analyses confirmed the microflora shifts towards enterobacteria during colitis and showed that the gut flora composition was similar in both, healthy wt and TLR-deficient animals.Conclusions and SignificanceDSS-induced colitis is characterized by a shift in the intestinal microflora towards pro-inflammatory Gram-negative bacteria. Bacterial products exacerbate acute inflammation via TLR2- and TLR4-signaling and direct the recruitment of neutrophils and regulatory T-cells to intestinal sites. E. coli may serve as a biomarker for colitis severity and DSS-induced barrier damage seems to be a valuable model to further identify bacterial factors involved in maintaining intestinal homeostasis and to test therapeutic interventions based upon anti-TLR strategies.
Highlights
In inflammatory bowel diseases (IBD) the disturbance of intestinal barrier functions results in increased immunoreactivity against bacterial antigens [1,2,3]
Severity of acute intestinal inflammation depends on TLR2- and TLR4-signaling
We have recently demonstrated that commensal E. coli increase and exacerbate small intestinal inflammation in C57BL/10 mice via LPS-mediated TLR4-signaling [8,14]
Summary
In inflammatory bowel diseases (IBD) the disturbance of intestinal barrier functions results in increased immunoreactivity against bacterial antigens [1,2,3]. Patients with active intestinal inflammation display accumulation of commensal Escherichia coli or Bacteroides spp. at inflamed tissue sites [4,5,6]. These bacterial groups, suspected to trigger intestinal inflammation in acute graft-versushost-disease after bone marrow transplantation [7], can further potentiate immunopathology by translocation via microlesions and ulcerations [5,8]. High numbers of E. coli in the inflamed ileum point towards an important role of bacterial lipopolysaccharide (LPS) in the exacerbation of acute intestinal inflammation. We have recently reported that Escherichia coli accumulates in murine ileitis and exacerbates small intestinal inflammation via Toll-like receptor (TLR) signaling. E. coli may serve as a biomarker for colitis severity and DSS-induced barrier damage seems to be a valuable model to further identify bacterial factors involved in maintaining intestinal homeostasis and to test therapeutic interventions based upon anti-TLR strategies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
