MECHANISMS OF ANTIDIARRHEAL EFFECT BY PROBIOTICS

Abstract

Gastroenteritis is a major cause of morbidity and mortality worldwide. Several microbial pathogens cause secretory diarrhea such as Vibrio cholerae and enterotoxigenic Escherichia coli as well as enteric viruses such as Rotavirus (RV) and Norovirus and parasites including Cryptosporidium. Other agents induce inflammatory diarrhea such as Clostridium difficile, Shigella and selected strains of pathogenic E. coli.Gastroenteritis is the result of multiple mechanisms that may mainly be summarized in enterotoxic (secretory diarrhea) or cytotoxic (osmotic diarrhea) as a consequence of ion secretion and epithelial damage, respectively. Other indirect mechanisms of infectious diarrhea include inflammation or altered regulatory processes involving hormones and neurotransmitters.The first‐line treatment of acute gastroenteritis in children is the administration of oral rehydration solution (ORS) but this neither shortens the duration of diarrhea nor reduces the frequency of stool outputs. Therefore, active therapies are now recommended in adjunct to ORS for children with gastroenteritis.The use of the specific probiotic strains, namely Lactobacillus rhamnosus GG (LGG) and Saccharomyces boulardii, is included ESPGHAN/ESPID guidelines for the management of children with AGE as an adjunct to rehydration therapy.Antidiarrheal drugs act at the luminal side of intestinal epithelium and modulate apical pathways, induce ion absorption or limit secretion, influence microbiome, modulate permeability, bind secretory moieties such as enterotoxins or bile acids. Probiotics are not drugs, but are rapidly effective in acute diarrhea reducing its duration and their effects have been linked to intestinal permeability and the modulation of intestinal microbiota and‐ indirectly‐ of inflammation. Those mechanisms are not consistent with the rapid effects of probiotics observed in children with acute diarrhea within hours since their initial administration. Evidence exists in favor of direct effects induced by probiotics on the enterocyte. Saccharomyces boulardii secreted moieties prevented RV‐induced oxidative stress and chloride secretion in human enterocytes. LGG exerted an ion proabsorptive effect through a direct antioxidant mechanisms and also promoted cell growth and differentiation acting on MAPKs. Those data indicate that the rapid and effective clinical effects by probiotics on acute diarrhea are probably the results of the direct microbe‐enterocyte rather than to the microbe‐microbiota or microbe‐immune interaction. This data provide an entirely new scenario for understanding the antidiarrheal mechanisms of probiotics in diarrhea.