Ca2+ fortified oral rehydration solution is effective in reducing diarrhea morbidity in cholera toxin-pretreated mice

Diarrhea like cholera remains a leading cause of mortality and morbidity globally. Oral rehydration solution (ORS) that developed in 1970s significantly decreases diarrhea mortality; yet, it does not reduce diarrhea morbidity and its usage has reduced persistently. Patients with diarrhea lose not only monovalent ions Na⁺, K⁺, Cl^- and HCO₃, which are replaced via ORS, but also divalent ions Zn²⁺ and Ca²⁺, which are not routinely replaced, particularly for Ca²⁺. Using several in vitro technologies performed in isolated tissues, we have previously shown that Ca²⁺, a primary ligand that activates the Ca²⁺-sensing receptor, can act on intestinal epithelium and enteric nervous system and reverse cholera toxin-induced fluid secretion. In the present study, using the cholera toxin-pretreated C57BL/6 mice as a model, we show that the anti-diarrheal effect of Ca²⁺ can also occur in vivo. Our results raise a question of whether this divalent ion also needs to be replaced in diarrhea management. Perhaps, an ideal rehydration therapy would be solutions that contain both monovalent ions, which reduce diarrhea mortality, and divalent minerals, which reduce diarrhea morbidity.