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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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Different antibiotic treatments lead to different degrees of                            intestinal pathology in 129S1/SvImJ mice.A. S. Typhimurium levels in caeca of 129S1/SvImJ mice                            after 4 days of infection with or without antibiotic treatment. B.                                S. Typhimurium levels in feces of 129S1/SvImJ mice                            after 4 days of infection with or without antibiotic treatment. C.                            H&E staining of caeca of 129S1/SvImJ mice. (a). infected 129S1/SvImJ                            mice; (b). metronidazole-treated and infected 129S1/SvImJ mice; (c).                            streptomycin-treated and infected 129S1/SvImJ mice; (d).                            vancomycin-treated and infected 129S1/SvImJ mice. D. Pathology scores of                            caeca of 129S1/SvImJ mice after 4 days of infection with or without                            antibiotic treatment. E. Levels of IL6 in caecal samples measured by                            ELISA. F. Levels of IL8 in caecal samples measured by ELISA. G. Levels                            of IFNγ in caecal samples measured by ELISA. Met: metronidazole (750                            mg/L), Strep: streptomycin (450 mg/L) and Vanco: vancomycin (50 mg/L).                            Black bars represent pathology scores of the intestinal lumen, white                            bars represent scores of the surface epithelia, dark grey bars represent                            scores of the mucosa and light grey bars represent scores of the                            submucosa of the tissue. 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-g001: Different antibiotic treatments lead to different degrees of intestinal pathology in 129S1/SvImJ mice.A. S. Typhimurium levels in caeca of 129S1/SvImJ mice after 4 days of infection with or without antibiotic treatment. B. S. Typhimurium levels in feces of 129S1/SvImJ mice after 4 days of infection with or without antibiotic treatment. C. H&E staining of caeca of 129S1/SvImJ mice. (a). infected 129S1/SvImJ mice; (b). metronidazole-treated and infected 129S1/SvImJ mice; (c). streptomycin-treated and infected 129S1/SvImJ mice; (d). vancomycin-treated and infected 129S1/SvImJ mice. D. Pathology scores of caeca of 129S1/SvImJ mice after 4 days of infection with or without antibiotic treatment. E. Levels of IL6 in caecal samples measured by ELISA. F. Levels of IL8 in caecal samples measured by ELISA. G. Levels of IFNγ in caecal samples measured by ELISA. Met: metronidazole (750 mg/L), Strep: streptomycin (450 mg/L) and Vanco: vancomycin (50 mg/L). Black bars represent pathology scores of the intestinal lumen, white bars represent scores of the surface epithelia, dark grey bars represent scores of the mucosa and light grey bars represent scores of the submucosa of the tissue. 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: In order to study the impact of antibiotic treatment on host susceptibility to infection, we treated 129S1/SvImJ mice with antibiotics in their drinking water before oral infection with S. Typhimurium. Four days post-infection, mice were sacrificed and samples from caecum, spleen and feces were analyzed. S. Typhimurium caecal colonization was increased over ten-fold in streptomycin-, vancomycin- and metronidazole-treated mice compared to control-infected mice (Figure 1A). S. Typhimurium counts were similar between mice treated with each of the different antibiotics. Colonization levels in feces were comparable to the counts obtained in caecal samples (Figure 1B). At the systemic level (spleen), S. Typhimurium counts did not significantly change after antibiotic treatment compared to the infected control mice (data not shown).


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)

Different antibiotic treatments lead to different degrees of                            intestinal pathology in 129S1/SvImJ mice.A. S. Typhimurium levels in caeca of 129S1/SvImJ mice                            after 4 days of infection with or without antibiotic treatment. B.                                S. Typhimurium levels in feces of 129S1/SvImJ mice                            after 4 days of infection with or without antibiotic treatment. C.                            H&E staining of caeca of 129S1/SvImJ mice. (a). infected 129S1/SvImJ                            mice; (b). metronidazole-treated and infected 129S1/SvImJ mice; (c).                            streptomycin-treated and infected 129S1/SvImJ mice; (d).                            vancomycin-treated and infected 129S1/SvImJ mice. D. Pathology scores of                            caeca of 129S1/SvImJ mice after 4 days of infection with or without                            antibiotic treatment. E. Levels of IL6 in caecal samples measured by                            ELISA. F. Levels of IL8 in caecal samples measured by ELISA. G. Levels                            of IFNγ in caecal samples measured by ELISA. Met: metronidazole (750                            mg/L), Strep: streptomycin (450 mg/L) and Vanco: vancomycin (50 mg/L).                            Black bars represent pathology scores of the intestinal lumen, white                            bars represent scores of the surface epithelia, dark grey bars represent                            scores of the mucosa and light grey bars represent scores of the                            submucosa of the tissue. 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-g001: Different antibiotic treatments lead to different degrees of intestinal pathology in 129S1/SvImJ mice.A. S. Typhimurium levels in caeca of 129S1/SvImJ mice after 4 days of infection with or without antibiotic treatment. B. S. Typhimurium levels in feces of 129S1/SvImJ mice after 4 days of infection with or without antibiotic treatment. C. H&E staining of caeca of 129S1/SvImJ mice. (a). infected 129S1/SvImJ mice; (b). metronidazole-treated and infected 129S1/SvImJ mice; (c). streptomycin-treated and infected 129S1/SvImJ mice; (d). vancomycin-treated and infected 129S1/SvImJ mice. D. Pathology scores of caeca of 129S1/SvImJ mice after 4 days of infection with or without antibiotic treatment. E. Levels of IL6 in caecal samples measured by ELISA. F. Levels of IL8 in caecal samples measured by ELISA. G. Levels of IFNγ in caecal samples measured by ELISA. Met: metronidazole (750 mg/L), Strep: streptomycin (450 mg/L) and Vanco: vancomycin (50 mg/L). Black bars represent pathology scores of the intestinal lumen, white bars represent scores of the surface epithelia, dark grey bars represent scores of the mucosa and light grey bars represent scores of the submucosa of the tissue. 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: In order to study the impact of antibiotic treatment on host susceptibility to infection, we treated 129S1/SvImJ mice with antibiotics in their drinking water before oral infection with S. Typhimurium. Four days post-infection, mice were sacrificed and samples from caecum, spleen and feces were analyzed. S. Typhimurium caecal colonization was increased over ten-fold in streptomycin-, vancomycin- and metronidazole-treated mice compared to control-infected mice (Figure 1A). S. Typhimurium counts were similar between mice treated with each of the different antibiotics. Colonization levels in feces were comparable to the counts obtained in caecal samples (Figure 1B). At the systemic level (spleen), S. Typhimurium counts did not significantly change after antibiotic treatment compared to the infected control mice (data not shown).

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