Investigating the Role of Isovalerate in Intestinal Barrier Maintenance




Pluzhnikova, Vicka

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"Helminth (parasitic worm) infections affect nearly a quarter of the world’s population and can last for decades. Helminths accomplish this by dampening the host’s immune response, and the associated mechanisms can be exploited for treatment of human allergic, inflammatory, and autoimmune diseases. Because helminths are known to alter the host gut microbiota composition, it is thought that helminth-induced immunomodulation is in part mediated by microbe-derived molecules. Previous lab members determined that a small molecule, the short-chain fatty acid (SCFA) isovalerate, is significantly upregulated during mouse Heligmosomoides polygyrus helminth infection. This phenomenon is specific to the proximal small intestine (PSI) where H. polygyrus localizes and induces epithelial damage. Because other SCFAs are known to promote intestinal barrier integrity and isovalerate is upregulated at a site of epithelial barrier damage, I hypothesize that isovalerate can promote epithelial barrier integrity in the PSI. I found that the expression of SCFA receptors FFAR2 and FFAR3, which mediate barrier-maintaining signalling, is unchanged and significantly upregulated, respectively, in infected mouse PSI. This suggests an increased capacity for receptor-mediated isovaleric signalling. Additionally, I established mouse models to test whether isovalerate can alleviate PSI barrier damage. Results will elucidate isovalerate’s potential use in human inflammatory bowel disease treatment."



helminth, immunomodulation, short-chain fatty acid, isovalerate, inflammatory bowel disease, small intestine