Oral rehydration solutions (ORS) remains the most cost-effective medical treatment, with the amalgamation of sugar, salt, and clean water reduces the mortality of toxigenic secretory diarrhoea 50-fold or more. ORS development has witnessed innumerable events, modifications and co-lateral discoveries on its way to the present world. 

The outbreak of the cholera pandemic in 1871 can be credited for the discovery of life-saving fluid ORS. With many more discoveries priorly, the year 1832 brought the idea of Intravenous hydration for severe cholera, proposed by Thomas Lata and others. They developed saline-based solutions for intravascular volume resuscitation for the treatment of cholera.

Robert Crane in 1960 discovered that luminal sodium ions increased the rate of transport of glucose in rat ileum, which is considered the foundation for the study of ion cotransport mechanisms. The year 1968 witnessed numerous publications of studies conducted in India and Pakistan reporting that glucose-containing solutions when perfused in the intestine via a long tube or consumed orally substantially decrease stool volume. Thus documenting the efficacy of ORS in epidemic cholera. 

Thus the revolutionary development of ORS can be credited to the year 1968 by David R. Nalin and others, who explained the efficacy of oral hydration for massive fluid losses and proposed ORS for epidemic diarrhoea and Pedialyte® for pediatric diarrhoea. 

This further lead to many publications documenting refinements of the original sodium-glucose-containing solution by the addition of organic components such as amino acids or fermentable polymers such as resistant starch with further improvement on recovery times and treatment success. 

Glucose co-transport studies, additionally lead to the discovery and cloning of the Na+:glucose co-transporter SGLT1 by Ernest Wright followed by the cloning and characterization of co-transporters for many nutrients and ions, and also to the development of SGLT2 inhibitors for diabetes.

Along with ORS, the cholera outbreak also leads to the discovery of bacterial enterotoxins and their mechanism of action. Dr. S. N. De, in 1959 reported that sterile filtrates of Vibrio choleræ induced fluid secretion in; perfused rabbit jejunal loops.

Another major scientific advance was reported in 1972 by Schafer et al. that cholera toxin increases intestinal cAMP levels, which provided the foundation for understanding the mechanism of exotoxin-induced intestinal fluid secretion. This further lead to the discovery that adenylate cyclase 6 is specifically induced by cholera toxin, providing a plausible target for translational studies. 

Another noticeable discovery was the development of small-molecule inhibitors of the cystic fibrosis transmembrane regulator (CFTR) anion channel, which have been useful, in vitro but are still struggling for their clinical usage in toxigenic diarrhoea.

The discovery of the mechanism of action of cholera toxin led to the formation of a class of drugs, the guanylate cyclase C (GC-C) receptor ligands that effectively treat constipation in IBS patients by mimicking the closely related prosecretory actions of E. coli heat-stable enterotoxin to produce cholera-like symptoms by inducing mucosal cGMP production.

Dr. Henry Binder was the first to describe the advantages of the inclusion of fermentable carbohydrate polymers in ORS. Dr. Zulfiqar A. Bhutta worries that ORS therapy is underused despite its unparalleled safety, efficacy, and low cost.

ORS needs promotion in its use in the developing world and can be considered potentially the most important medical advance this century.

Source: Kaunitz JD. Oral Defense: How Oral Rehydration Solutions Revolutionized the Treatment of Toxigenic Diarrhea. Dig Dis Sci. 2020;65(2):345-348. doi:10.1007/s10620-019-06023-5