Influence of stressor-induced nervous system activation on the intestinal microbiota and the importance for immunomodulation

Abstract

The body is colonized by a vast population of genetically diverse microbes, the majority of which reside within the intestines to comprise the intestinal microbiota. During periods of homeostasis, these microbes reside within stable climax communities, but exposure to physical, physiological, as well as psychological stressors can significantly impact the structure of the intestinal microbiota. This has been demonstrated in humans and laboratory animals, with the most consistent finding being a reduction in the abundance of bacteria in the genus Lactobacillus. Whether stressor exposure also changes the function of the microbiota, has not been as highly studied. The studies presented in this review suggest that stressor-induced disruption of the intestinal microbiota leads to increased susceptibility to enteric infection and overproduction of inflammatory mediators that can induce behavioral abnormalities, such as anxiety-like behavior. Studies involving germfree mice also demonstrate that the microbiota are necessary for stressor-induced increases in innate immunity to occur. Exposing mice to a social stressor enhances splenic macrophage microbicidal activity, but this effect fails to occur in germfree mice. These studies suggest a paradigm in which stressor exposure alters homeostatic interactions between the intestinal microbiota and mucosal immune system and leads to the translocation of pathogenic, and/or commensal, microbes from the lumen of the intestines to the interior of the body where they trigger systemic inflammatory responses and anxiety-like behavior. Restoring homeostasis in the intestines, either by removing the microbiota or by administering probiotic microorganisms, can ameliorate the stressor effects.