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Abstract

In the current thesis work, we set out to understand how the host microbiota, intestinal epithelial cells, and immune system work together to promote barrier integrity and intestinal homeostasis. Using 16S Sequencing and metabolomic analyses we were able to show that secretory immunoglobulins, such as IgA, can support microbial function. In particular, secretory immunoglobulins promoted the production of short-chain fatty acids by the colonic microbiota. In particular, we show that secretory immunoglobulins support a greater abundance of butyrate-producing microbes in the colonic microbiota. In this work, we also showed that microbially dependent HSP25/27 promoted intestinal wound healing during acute colitis, highlighting a novel role of HSP in promoting intestinal restitution. We showed that HSP25/27 was critical in the maintenance of phosphorylated STAT3 (pSTAT3). Maintenance of pSTAT3 supports the transcription factors ability to promote epithelial cell proliferation. We also showed that HSP25/27 supports filamentous actin polarization, consequently influencing the ability of epithelial to migrate during wound healing. Together, the work provides novel insight into how interactions between the immune system, the intestinal microbiota, and intestinal epithelial cells support one another to promote barrier integrity.

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