Beneficial Modulation of the Gut Microbiota Prevents Stress-Induced Adverse Effects

Abstract

The gut microbiota plays a significant role in maintaining the homeostasis and overall health status of the host. Moreover, it has been shown that heat stress severely alters the stability of the gut microbiota. Thus, negative alterations of the gut microbiota, known as dysbiosis, have been linked to a plethora of disorders. One in particular, is the dysfunction of the intestinal barrier integrity, which results in increased intestinal permeability and translocation of toxic bacterial components, such as lipopolysaccharides (LPS), from the gut lumen into the circulation. Elevated intestinal permeability can cause tissue injury, multi-organ dysfunction, and even death. Therefore, the stability of the gut microbiota is key in maintaining homeostasis and, as a result, the ability of the host to tolerate stress. Various approaches that modulate the gut microbiota, such as probiotics and prebiotics, have been proposed to prevent dysbiosis and dysbiosis related disorders. In this work, we examined the adverse effects generated by both environmental and metabolic heat stress on the morphology and function of the intestinal barrier. Then, we evaluated the efficacy of a Bacillus subtilis probiotic strain and Saccharomyces cerevisiae fermentate, as a prebiotic, in preventing the loss of the integral intestinal barrier function and maintaining the gut microbiota caused by heat stress. Animals were pre-treated by oral gavage with either a Bacillus subtilis probiotic strain, or Saccharomyces cerevisiae fermentate, or phosphate buffered saline (PBS) prior to exposure to heat stress. Morphological changes in the gastrointestinal tract gut of rats and the expression of intestinal tight junction proteins as a result of heat stress were altered in stressed animals treated with PBS. There were significant disruptions in the morphological structure: decrease of villi height, total mucosal thickness, decreases in the number of Paneth and goblet cells, and reduced expression of tight junction proteins (Zonula occludence (ZO-1), occludin, claudin, junctional adhesion molecule A (JAM-A)). In addition, the serum of those experimental animals displayed significant elevation levels of pro-inflammatory cytokines, and markers of intestinal barrier dysfunction such as lipopolysaccharides (LPS). Culture-based and Tag-Encoded FLX Amplicon Pyrosequencing analysis of the gut microbiota demonstrated significant perturbations of the gut microbiota, with increases in pathobionts and reduction of beneficial species. Administration of probiotic and prebiotic prevented all registered disorders. Our results demonstrate the efficacy of Bacillus subtilis probiotic strain and Saccharomyces cerevisiae fermentate treatment in protecting the stability of the gut microbiota and preventing harmful effects of heat stress. We speculate that this approach can be utilized to treat and prevent the loss of the intestinal barrier observed in pathologies other than heat stress.