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

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.

SUBMITTER: Ferreira RB

PROVIDER: S-EPMC3102097 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The pathological mechanisms of gastrointestinal disorders, including inflammatory bowel disease (IBD), in pigs are poorly understood. We report the induction of intestinal inflammation in heat-stressed (HS) pigs, fecal microbiota transplantation from pigs to mice, and explain the role of microorganisms in IBD. 24 adult pigs were subjected to HS (34 ± 1 °C; 75-85% relative humidity for 24h) while 24 control pigs (CP) were kept at 25 ± 3°C and the same humidity. Pigs were sacrificed on days 1, 7, 14, 21. Colonic content microbiome analyses were conducted. Pseudo-germ-free mice were fed by gavage with fecal microbiota from HS-pigs and CP to induce pig-like responses in mice. From 7 d, HS-pigs exhibited fever and diarrhea, and significantly lower colonic mucosal thickness, crypt depth/width, and goblet cell number. Compared with each control group, the concentration of cortisol in the peripheral blood of HS pigs gradually increased, significantly so on days 7, 14, and 21 (P < 0.01). While the concentration of LPS in HS pigs' peripheral blood was significantly higher on days 7, 14 (P < 0.01), and 21 (P < 0.05) compared with that of the control group. The colonic microbiome composition of HS-pigs was different to that of CP. By day 14, opportunistic pathogens (e.g., Campylobacterales) had increased in HS-pigs. The composition of the colonic microbiome in mice administered feces from HS-pigs was different from those receiving CP feces. Bacteroides were significantly diminished, Akkermansia were significantly increased, and intestinal damage and goblet cell numbers were higher in mice that received HS-pig feces. Moreover, we verified the relevance of differences in the microbiota of the colon among treatments. Heat stress promotes changes in gut microbiome composition, which can affect the colonic microbial structure of mice through fecal microbiota transplantation; the molecular mechanisms require further investigation. This study enhanced our understanding of stress-induced inflammation in the colon and the increase in diarrhea in mammals subjected to prolonged HS. Our results provide useful information for preventing or ameliorating deficits in pig production caused by prolonged exposure to high temperatures.

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

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