In CF patients CFTR function is partially or completely lost. CFTR is essential for the transport of chloride and bicarbonate across the epithelial cells of lungs, pancreas, liver, and intestine. Clinical tests capable of measuring CFTR-dependent bicarbonate transport in CF patients and its repair by CFTR rescue drugs are presently lacking. Main objectives of this project are to fill this gap by designing and validating an improved version of existing tests that allow assessment of the bicarbonate transport defect in CF at the intestinal level; further, to investigate whether novel CFTR corrector drugs, known to restore chloride transport in CF in a mutation-specific manner, are also capable of restoring bicarbonate transport and preventing the development of viscous mucus. The new test will be performed by using organoids (miniguts) derived from stem cells coming from CF patient rectal biopsies.