Dysbiosis, i.e. the alteration of the gut microbiota, as well as alterations of the gastrointestinal (GI) barrier, play a crucial role in human health and disease. The interest in elucidating the role of such conditions in diseases is growing, also due to the wide possibility of intervention to heal the gut function. In parallel, there is an increasing demand for effective methods aimed to evaluation of dysbiosis and GI barrier alterations, in a non invasive and cost-effective manner, since this is needed both for baseline patient characterization and for monitoring patient¿s response to therapeutic interventions.
The proposed project aims to: i) improve the existing assays for diagnosis of dysbiosis by development of an LC-MS/MS method to determine urinary concentration of metabolites produced by the intestinal microbiota, which are related with specific subtypes of dysbiosis and, ii) to improve the diagnosis of GI barrier damage, by integration of the standard lactulose/mannitol (L/M) absorption test with a novel assay measuring serum concentration of tight junctions¿ protein, which represent an index of GI barrier breakage. This serum protein test will be developed using a new technology for multiplex detection of analytes in suspension , the PlexBio Precision Imange Code microdiscs with the PlexBio Analyzer.
Furthermore, the developed metabolites/proteins assays will be employed to characterized the dysbiosis/intestinal permeability profile in a group of healthy subjects and in a group of metastatic non-small cell lung cancer patients treated with afatinib, a drug with important GI toxicity. Association between urinary/serum concentration of the analyzed markers will be studied to detect possible relations with the individual risk of GI toxicity during treatment with afatinib and also with the therapy outcome, since metabolic reactions by microbiota and GI barrier damage may affect absorption of orally administrated medications.
