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Studies on the influence of urolithin - bioavailable metabolites of the human intestinal flora on the molecular processes related to the suppression of inflammation.

Project Title
Badania wpływu urolityn- biodostępnych metabolitów flory jelitowej człowieka na molekularne procesy związane z wygaszaniem stanu zapalnego.
Financing Institution
Lead
dr Jakub Patryk Piwowarski
Project Objective

The human intestinal flora is of key importance for health mainly through its influence on the immune system and the metabolism of nutrients and xenobiotics. One of the groups of compounds that undergo significant structural changes under its influence are ellagotanoids, which are macromolecular polyphenols found in walnuts, pomegranate juice, raspberries, strawberries or wine matured in barrels. The positive effects of consuming these products on the circulatory system and non-specific inflammation of the large intestine are particularly emphasized, and due to the metabolism of ellagotanoids by the intestinal flora in recent years, it is postulated that bioavailable urolithins produced in the intestine may be responsible for the observed effects. As a significant role in the pathophysiology of the above diseases is played by disruptions in the functioning of mechanisms related to the active suppression of inflammation, the aim of the project will be to investigate the influence of urolithins on the molecular processes underlying this phenomenon. Comparative in vitro studies of the effect of urolithins and their phase II metabolites: glucuronides and sulphates (obtained from the urine of volunteers consuming ellagotanoid-rich products) on neutrophil apoptosis, phagocytosis of neutrophils by macrophages (eferocytosis) and the secretion of anti-inflammatory factors by macrophages will be carried out. Additionally, the hydrolysis of urolithin glucuronides under the influence of glucuronidase released by stimulated neutrophils and macrophages will be investigated. Demonstrating the effect of urolithines on the active suppression of inflammation will contribute to the confirmation of the therapeutic efficacy of ellagotanoid-rich products in diseases associated with chronic inflammation and will allow to indicate the molecular mechanisms of action responsible for these effects.