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Volemic control is essential for maintaining tissue perfusion and fluid homeostasis, with cardiorenal and endothelial mediators regulating intravascular composition, often impaired in pathological states. Notably, intestinal epithelial cells are highly sensitive to volume fluctuations, resulting in changes in intestinal permeability that may not be detected by current diagnostic methods. This review offers a comprehensive description of the main mediators involved in volemic regulation, their impact on intestinal morphofunctionality, and specific details regarding epithelial cells. Additionally, key biomarkers - especially lactulose/mannitol - for assessing intestinal barrier disruption are highlighted, and a novel approach is proposed using liquid chromatography-mass spectrometry to investigate gut alterations in heart failure and exercise-induced stress, which are silent and neglected conditions with significant repercussions on intestinal barrier function.