Molecular mechanisms of probiotic prevention of antibiotic-associated diarrhea

Abstract

Antibiotic-associated diarrhea (AAD) is a common and unintended adverse effect of antibiotic treatment. It is characterized by the disruption of the gut microbiota, decreased intestinal short chain fatty acid (SCFA) concentrations, accumulation of luminal carbohydrates and colonic bile acids, altered water absorption, and ultimately diarrhea. Probiotics were shown to prevent AAD in numerous clinical trials. This review examines what is currently known about how probiotics reduce the risk for AAD via modulating the gut microbiota, altering nutrient and bile acid metabolism, inducing epithelial solute transporter activity, supporting intestinal barrier function, and influencing the immune system. Although probiotics are frequently prescribed with antibiotic use, mechanistic evidence verifying how they confer protection against AAD is extremely limited. This information is urgently needed for improving recommendations for sustaining probiotic development and for implementing probiotics in clinical settings.

Figure 1.. Schematic model of the potential molecular mechanisms responsible for probiotic prevention of AAD.

Antibiotic treatment disrupts the composition of the GI tract microbiota, leading to increased growth of opportunistic pathogens, the accumulation of undigested carbohydrates, and reduced levels of SCFAs and modified bile acids. Probiotics might counter antibiotic-induced effects in the GI tract by directly impairing pathogen growth or by inducing other alterations to gut microbiota composition via SCFA synthesis, production of other secreted metabolites such as bacteriocins, or by reducing lumenal pH and O2 levels. Probiotics might also cause changes to bile acid composition as well as directly interact with the intestinal epithelium and immune system to result in increased gut barrier function and modulation of water and solute transport.