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The intestinal microbiota plays a role in Salmonella-induced colitis independent of pathogen colonization.

Ferreira RB, Gill N, Willing BP, Antunes LC, Russell SL, Croxen MA, Finlay BB - PLoS ONE (2011)

Bottom Line: Although all antibiotic treatments caused similar increases in pathogen colonization, the development of enterocolitis was seen only when streptomycin or vancomycin was used; no significant pathology was observed with the use of metronidazole.Our data suggests that different members of the microbiota might be associated with S.Dissecting the mechanisms involved in resistance to infection and inflammation will be critical for the development of therapeutic and preventative measures against enteric pathogens.

View Article: PubMed Central - PubMed

Affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada.

ABSTRACT
The intestinal microbiota is composed of hundreds of species of bacteria, fungi and protozoa and is critical for numerous biological processes, such as nutrient acquisition, vitamin production, and colonization resistance against bacterial pathogens. We studied the role of the intestinal microbiota on host resistance to Salmonella enterica serovar Typhimurium-induced colitis. Using multiple antibiotic treatments in 129S1/SvImJ mice, we showed that disruption of the intestinal microbiota alters host susceptibility to infection. Although all antibiotic treatments caused similar increases in pathogen colonization, the development of enterocolitis was seen only when streptomycin or vancomycin was used; no significant pathology was observed with the use of metronidazole. Interestingly, metronidazole-treated and infected C57BL/6 mice developed severe pathology. We hypothesized that the intestinal microbiota confers resistance to infectious colitis without affecting the ability of S. Typhimurium to colonize the intestine. Indeed, different antibiotic treatments caused distinct shifts in the intestinal microbiota prior to infection. Through fluorescence in situ hybridization, terminal restriction fragment length polymorphism, and real-time PCR, we showed that there is a strong correlation between the intestinal microbiota composition before infection and susceptibility to Salmonella-induced colitis. Members of the Bacteroidetes phylum were present at significantly higher levels in mice resistant to colitis. Further analysis revealed that Porphyromonadaceae levels were also increased in these mice. Conversely, there was a positive correlation between the abundance of Lactobacillus sp. and predisposition to colitis. Our data suggests that different members of the microbiota might be associated with S. Typhimurium colonization and colitis. Dissecting the mechanisms involved in resistance to infection and inflammation will be critical for the development of therapeutic and preventative measures against enteric pathogens.

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MIB and Lactobacillus sp. levels are associated to                            predisposition to S. Typhimurium-induced                            colitis.A. Levels of MIB on fecal samples of 129S1/SvImJ and C57BL/6 mice before                            and after antibiotic treatment, as determined by RT-PCR. B. Levels of                                Lactobacillus on fecal samples of 129S1/SvImJ and                            C57BL/6 mice before and after antibiotic treatment, as determined by                            RT-PCR. ns: not significant; *: p<0.05;                            **: p<0.01; ***: p≤0.001. Experiments were                            performed three times with at least 4 mice in each group.
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pone-0020338-g006: MIB and Lactobacillus sp. levels are associated to predisposition to S. Typhimurium-induced colitis.A. Levels of MIB on fecal samples of 129S1/SvImJ and C57BL/6 mice before and after antibiotic treatment, as determined by RT-PCR. B. Levels of Lactobacillus on fecal samples of 129S1/SvImJ and C57BL/6 mice before and after antibiotic treatment, as determined by RT-PCR. ns: not significant; *: p<0.05; **: p<0.01; ***: p≤0.001. Experiments were performed three times with at least 4 mice in each group.

Mentions: Real-time PCR was used to confirm the results of TRFLP and clone-library data, and to further characterize the abundance of specific bacterial subsets that were below detection levels of community profiling techniques. Because of the differences in the Bacteroidetes numbers between the groups predisposed or resistant to colitis, we investigated the levels of Mouse Intestinal Bacteria (MIB) [11], a subset of Porphyromonadaceae, in these mice. We also confirmed the results obtained by TRFLP, which showed a prevalence of TRF188, identified as Lactobacillus sp., in samples of mice predisposed to colitis. We observed that MIB levels did not significantly change after streptomycin treatment of 129S1/SvImJ or metronidazole treatment of C57BL/6 mice, both models that are predisposed to colitis. In contrast, MIB levels were significantly increased after metronidazole treatment of 129S1/SvImJ (Figure 6A). The opposite was seen when we analyzed Lactobacillus numbers, which increased after streptomycin (colitis-inducing) but not metronidazole (colitis non-inducing) treatment of 129S1/SvImJ (Figure 6B).


The intestinal microbiota plays a role in Salmonella-induced colitis independent of pathogen colonization.

Ferreira RB, Gill N, Willing BP, Antunes LC, Russell SL, Croxen MA, Finlay BB - PLoS ONE (2011)

MIB and Lactobacillus sp. levels are associated to                            predisposition to S. Typhimurium-induced                            colitis.A. Levels of MIB on fecal samples of 129S1/SvImJ and C57BL/6 mice before                            and after antibiotic treatment, as determined by RT-PCR. B. Levels of                                Lactobacillus on fecal samples of 129S1/SvImJ and                            C57BL/6 mice before and after antibiotic treatment, as determined by                            RT-PCR. ns: not significant; *: p<0.05;                            **: p<0.01; ***: p≤0.001. Experiments were                            performed three times with at least 4 mice in each group.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3102097&req=5

pone-0020338-g006: MIB and Lactobacillus sp. levels are associated to predisposition to S. Typhimurium-induced colitis.A. Levels of MIB on fecal samples of 129S1/SvImJ and C57BL/6 mice before and after antibiotic treatment, as determined by RT-PCR. B. Levels of Lactobacillus on fecal samples of 129S1/SvImJ and C57BL/6 mice before and after antibiotic treatment, as determined by RT-PCR. ns: not significant; *: p<0.05; **: p<0.01; ***: p≤0.001. Experiments were performed three times with at least 4 mice in each group.
Mentions: Real-time PCR was used to confirm the results of TRFLP and clone-library data, and to further characterize the abundance of specific bacterial subsets that were below detection levels of community profiling techniques. Because of the differences in the Bacteroidetes numbers between the groups predisposed or resistant to colitis, we investigated the levels of Mouse Intestinal Bacteria (MIB) [11], a subset of Porphyromonadaceae, in these mice. We also confirmed the results obtained by TRFLP, which showed a prevalence of TRF188, identified as Lactobacillus sp., in samples of mice predisposed to colitis. We observed that MIB levels did not significantly change after streptomycin treatment of 129S1/SvImJ or metronidazole treatment of C57BL/6 mice, both models that are predisposed to colitis. In contrast, MIB levels were significantly increased after metronidazole treatment of 129S1/SvImJ (Figure 6A). The opposite was seen when we analyzed Lactobacillus numbers, which increased after streptomycin (colitis-inducing) but not metronidazole (colitis non-inducing) treatment of 129S1/SvImJ (Figure 6B).

Bottom Line: Although all antibiotic treatments caused similar increases in pathogen colonization, the development of enterocolitis was seen only when streptomycin or vancomycin was used; no significant pathology was observed with the use of metronidazole.Our data suggests that different members of the microbiota might be associated with S.Dissecting the mechanisms involved in resistance to infection and inflammation will be critical for the development of therapeutic and preventative measures against enteric pathogens.

View Article: PubMed Central - PubMed

Affiliation: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada.

ABSTRACT
The intestinal microbiota is composed of hundreds of species of bacteria, fungi and protozoa and is critical for numerous biological processes, such as nutrient acquisition, vitamin production, and colonization resistance against bacterial pathogens. We studied the role of the intestinal microbiota on host resistance to Salmonella enterica serovar Typhimurium-induced colitis. Using multiple antibiotic treatments in 129S1/SvImJ mice, we showed that disruption of the intestinal microbiota alters host susceptibility to infection. Although all antibiotic treatments caused similar increases in pathogen colonization, the development of enterocolitis was seen only when streptomycin or vancomycin was used; no significant pathology was observed with the use of metronidazole. Interestingly, metronidazole-treated and infected C57BL/6 mice developed severe pathology. We hypothesized that the intestinal microbiota confers resistance to infectious colitis without affecting the ability of S. Typhimurium to colonize the intestine. Indeed, different antibiotic treatments caused distinct shifts in the intestinal microbiota prior to infection. Through fluorescence in situ hybridization, terminal restriction fragment length polymorphism, and real-time PCR, we showed that there is a strong correlation between the intestinal microbiota composition before infection and susceptibility to Salmonella-induced colitis. Members of the Bacteroidetes phylum were present at significantly higher levels in mice resistant to colitis. Further analysis revealed that Porphyromonadaceae levels were also increased in these mice. Conversely, there was a positive correlation between the abundance of Lactobacillus sp. and predisposition to colitis. Our data suggests that different members of the microbiota might be associated with S. Typhimurium colonization and colitis. Dissecting the mechanisms involved in resistance to infection and inflammation will be critical for the development of therapeutic and preventative measures against enteric pathogens.

Show MeSH
Related in: MedlinePlus