<b>Responses of intestinal organoids to infection by</b> <i> <b>Mycobacterium avium</b> </i> <b>resemble symptoms observed in Crohn’s disease</b>

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD). <i>Mycobacterium avium</i>, which causes Johne's disease in ruminants, has been suggested as a potential CD trigger due to shared pathology, but early epithelial responses remain unclear. This study established a mouse small intestinal organoid (mSIO) model of <i>M. avium</i> infection to assess CD-related inflammation. Infected mSIOs were examined by confocal microscopy, block-face scanning electron microscopy, and macrophage co-culture to track bacterial localization and immune cell behavior. The data give unprecedent dynamic and super high resolution insights in the responses of gut cells to mycobacterial infection. RNA-seq with GSEA revealed strong induction of inflammatory genes and enrichment of pro-inflammatory pathways. Comparative analysis with CD-humanized mouse data showed overlapping gene expression and enrichment of the IBD signaling pathway. Notably, <i>Mmp7</i>, which can be linked to epithelial remodeling and inflammation, was a common marker in both models. This study presents a robust mSIO model of <i>M. avium</i> infection that recapitulates features of CD-associated inflammation both with high-resolution imaging and transcriptomics and identifies <i>Mmp7</i> as a potential molecular link between infection and CD-like pathology.