Gastrointestinal epithelial cells shed into digestive fluids constitute a reliable source of information on the epithelium physiology. Non-apoptotic epithelial cells have to survive into an environment poor in oxygen and nutrients by triggering ATP saving processes along with activation of the autophagic pathway. Sample handling and isolation strategies are critically detailed with a series of guidelines to assist in selecting and implementing an appropriate method to derive relevant biomedical information from DNA, transcripts and proteins of exfoliated phenotypes.