Leaky gut mechanisms in giardiasis

Abstract Giardia duodenalis is a common intestinal pathogen transmitted via consumption of contaminated water. In addition to causing distress symptoms, infection one the top 5 infectious causes growth stunting in children under two. Growth faltering complex pathology facilitated by changes barrier and enzymatic deficiencies. While widely associated with damage vitro, animal models, patient studies, mechanisms behind this process are not well understood. Since PAR2 has prominent role increased permeability Celiac disease, we focusing on involvement protease activated receptor 2 (PAR2) giardiasis-facilitated defects. We using human cell lines, murine organoids, mouse model address PAR2. Co-culture Caco2 cells results altered tight junction morphology as revealed staining for ZO-1; these reduced treatment antagonist. Effects signaling function being assessed measuring transepithelial electrical resistance (TEER) PAR2+/− PAR2−/− organoids cultured transwell filters. Additionally, while C57BL/6 mice fed low-protein diet exhibit weight gain when infected Giardia, lacking normally infected. These data indicate that contributes defects faltering. Identifying parasite factors activate will provide novel targets development pharmaceuticals vaccines improve child growth. AI166467