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Diarrheal disease is the second leading cause of death in children under 5\u00a0years of age, and globally, 1.7\u00a0billion cases of childhood diarrhea are reported every year. Accompanying diarrheal episodes are a number of secondary effects in gut physiology and structure, such as erosion of the mucosal barrier that lines the gut, facilitating further inflammation of the gut in response to the normal microbiome. Here, we focus on pathogenic bacteria\u2010mediated diarrhea, emphasizing the role of cyclic adenosine 3',5'\u2010monophosphate\u00a0and cyclic guanosine 3\u2032,5\u2032\u2010monophosphate in driving signaling outputs that result in the secretion of water and ions from the epithelial cells of the gut. 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