Colonic microbiota alters host susceptibility to infectious colitis by modulating inflammation, redox status, and ion transporter gene expression

Abstract

Individuals vary in their resistance to enteric infections. The role of the intestinal microbiota in altering susceptibility to enteric infection is relatively unknown. Previous studies have identified that C3H/HeOuJ mice suffer 100% mortality during Citrobacter rodentium-induced colitis, whereas C57BL/6 mice recover from infection. The basis for their differences in susceptibility is unclear and has been mainly attributed to differences in host genetics. This study investigated the role of the intestinal microbiota in altering susceptibility to C. rodentium-induced colitis. When the feces of C57BL/6 mice were gavaged into antibiotic treated C3H/HeOuJ mice, the C57BL/6 microflora led to a complete reversal in mortality patterns where 100% of the C3H/HeOuJ mice survived infection. This protection corresponded with reduced colonic pathology and less systemic pathogen load and was associated with increased inflammatory and redox responses with reduced epithelial cell death. C3H/HeOuJ mice are normally susceptible to infection-induced dehydration due to defective expression of colonic ion transporters such as Dra, CA IV, and CA I; expression of these genes was normalized when C3H/HeOuJ mice were colonized with the C57BL/6 microflora. Together, these data reveal that the colonic microbiota play a critical role in protecting against intestinal infection by inducing proinflammatory and prooxidant responses that control pathogen load as well as ion transporter gene expression previously shown to prevent fatal dehydration. Protection of mice from lethal colitis was associated with higher levels of bacteria from Bacteroidetes. This study reveals that the microbiota is sufficient to overcome inherent genetic susceptibility patterns in C3H/HeOuJ mice that cause mortality during C. rodentium infection.

Prolonged antibiotic treatment induces a diabetogenic intestinal microbiome that accelerates diabetes in NOD mice

“…We generated four groups of chimeric mice Figure 2a) by treating hosts with a combination of antibiotics followed by oral gavage of stool from donor mice as previously described (Ghosh et al, 2011). Normally, NOR mice develop limited insulitis (Prochazka et al, 1992), however, when transplanted with microbiota from NOD mice, the NOR H +NOD M mice displayed greater insulitis compared with control NOR H +NOR M mice (Figures 2b-d).…”

“…Similar to the approach of Ghosh et al (2011), for fecal transplantation experiments, NOD and NOR mice were treated with antibiotics (500 mg/l vancomycin, 1 g l − 1 neomycin, 1 g l − 1 ampicillin and 1 g l − 1 metronidazole) in drinking water from 4-8 weeks of age. Stool from donor mice (100 mg in 1.2 ml phosphate-buffered saline) was orally gavaged into recipient mice four times over 12 days starting at 8 weeks of age, creating chimeric mice (Figure 2a).…”

The interplay between microbiome dynamics and pathogen dynamics in a murine model ofClostridium difficileInfection

“…6,7 Therefore, changes in the gut microbiota, can influence the response to pathogens by altering the nature of host immunity. 48,49 Another mechanism by which altered gut microbial communities could affect a pathogen is by changing the overall opposing processes that are thought to be at the center of the pathogenesis of CDI ( fig. 8).…”

Probiotic Lactobacillus reuteri Attenuates the Stressor-Enhanced Severity of Citrobacter rodentium Infection

“…Strains that develop only subclinical symptoms, such as CD-1 and C57BL/6, are considered resistant to C. rodentium-induced infectious colitis, while mice that succumb to infection by C. rodentium, such as FVB/N and C3H/HeJ mice, are deemed susceptible (1,4,5). While it is recognized that host genetics contributes to enhanced susceptibility (4,5), recent data indicate that the colonic microbiota also modulates host susceptibility to C. rodentium, in part by altering mucosal immunity (6)(7)(8). Antibiotic treatment can disrupt the natural balance of the microbiota, which can leave mice more susceptible to C. rodentium infection (9).…”