Validation of a microbiome dependent colitis model via fecal microbial transplant in germ-free IL-10 deficient mice.

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Presentation Time: 10:30 AM - 10:45 AM
Abstract ID: 4398 - B

Presenting Author:
Caitlin Parello , Associate Director of Research Operations

Abstract:

Inflammatory Bowel Diseases (IBD) are immune-mediated intestinal tract diseases with undefined etiologies. Proposed pathogenic mechanisms include abnormal inflammatory response to the intestinal microbiome. Mice deficient in IL-10, a critical cytokine for mucosal immune homeostasis, spontaneously develop enterocolitis; phenotypes are microbiome-sensitive. To establish a microbiome-dependent colitis model with improved construct validity and translational clinical relevance, we assessed colitis development in Germ-Free IL-10 knockout mice (GF IL-10 KO; Taconic Biosciences) following inoculation with fecal microbial transplant (FMT) from wild-type C57BL/6NTac mice at the Murine Pathogen Free™ (MPF™) health standard and assessed clinical responses to anti-IL-12/23p40 (anti-p40). Compared to control GF IL-10 KO mice, FMT-inoculated mice demonstrated reduced weight gain, elevated levels of fecal lipocalin 2 and calprotectin, and increased colon weight:length ratio at 8 weeks following FMT. FMT-inoculated mice also showed elevated histopathology scores, increased colonic CD3+ T cells and CD4+ T_H cells, and epithelial hyperplasia by Ki-67 immunolabeling. Several colon cytokines were elevated in FMT-inoculated mice. Anti-p40 treatment significantly reduced all of these disease indicators with the exception of colon weight:length. These data provide a validated colitis model with relevant mechanisms for assessing the role of the microbiome and response to therapeutics in IBD.