Pre-treatment with Bifidobacterium breve UCC2003 modulates Citrobacter rodentium-induced colonic inflammation and organ specificity

Abstract

Citrobacter rodentium, which colonizes the gut mucosa via formation of attaching and effacing (A/E) lesions, causes transmissible colonic hyperplasia. The aim of this study was to evaluate whether prophylactic treatment with Bifidobacterium breve UCC2003 can improve the outcome of C. rodentium infection. Six-week-old albino C57BL/6 mice were pre-treated for 3 days with B. breve, challenged with bioluminescent C. rodentium and administered B. breve or PBS-C for 8 days post-infection; control mice were either administered B. breve and mock-infected with PBS, or mock-treated with PBS-C and mock-infected with PBS. C. rodentium colonization was monitored by bacterial enumeration from faeces and by a combination of both 2D bioluminescence imaging (BLI) and composite 3D diffuse light imaging tomography with µCT imaging (DLIT-µCT). At day 8 post-infection, colons were removed and assessed for crypt hyperplasia, histology by light microscopy, bacterial colonization by immunofluorescence, and A/E lesion formation by electron microscopy. Prophylactic administration of B. breve did not prevent C. rodentium colonization or A/E lesion formation. However, this treatment did alter C. rodentium distribution within the large intestine and significantly reduced colonic crypt hyperplasia at the peak of bacterial infection. These results show that B. breve could not competitively exclude C. rodentium, but reduced pathogen-induced colonic inflammation.

4D Multimodality Imaging of <em>Citrobacter rodentium</em> Infections in Mice

“…This technique facilitates the detailed analysis of how an infection spreads through an individual mouse and can be used to investigate how deletion of host or bacterial genes or particular intervention strategies effect bacterial load, distribution, and localization during a longitudinal study 7 . These videos also provide useful teaching aids and a means of disseminating information to the public.…”

“…Small animal models, in particular those utilizing mice, are routinely used to investigate bacterial pathogenesis or to test intervention strategies for infections, such as antibiotics, probiotics, prebiotics and vaccines [1][2][3][4][5][6][7] . The main experimental readouts from small animal infections are pathogen load, spatial and temporal localization of the infection, and changes to the immune response of the infected organism.…”

“…Recently, we used a combination of DLIT co-registered with μCT imaging to evaluate Citrobacter rodentium (C. rodentium) colonization dynamics following prophylactic treatment with a probiotic bacterium 7 . C. rodentium is a murine specific enteric pathogen used to model human infection with enteropathogenic and enterhemorrhagic Escherichia coli 4.…”

“…The exact anatomical localization of the BL foci in vivo has to be determined through the ex vivo analysis of organs 3,6,9 In contrast, composite 3D diffuse light imaging tomography (DLIT) can be used to compile a quantitative 3D reconstruction of the BL source 12 . DLIT is performed by collecting BL images taken using defined narrow band-pass optical filters and subsequently inputting them into a diffuse optical tomography 3D reconstruction algorithm 1,7,12,13 .…”

Intestinal flora of FAP patients containing APC-like sequences

“…C. rodentium-induced transmissible murine colonic hyperplasia model provides an excellent template to study how alterations in intestinal stem cells promote trans-differentiation and colon carcinogenesis following bacterial infection [15,16]. Although C. rodentium is not a human pathogen, the bacterial genes (35 kbp pathogenicity island) required for infection and presumably for the induction of epithelial cell hyperplasia are genetically similar to enteropathogenic and enterohemorrhagic Escherichia coli [14].…”