Stress and gut microbiota: Does postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response?

Indigenous microbiota have several beneficial effects on host physiological functions; however, little is known about whether or not postnatal microbial colonization can affect the development of brain plasticity and a subsequent physiological system response. In a series of experiments using germ-free (GF), specific pathogen-free (SPF), and gnotobiotic mice, we recently demonstrated that gut microbes could affect the development of hypothalamic-pituitary-adrenal (HPA) reaction to stress. In this study, in order to further verify these findings, we performed glucocorticoid-suppression test in GF and SPF mice. In addition, norepinephrine (NE), serotonin (5-HT), and γ-aminobutyric acid (GABA) levels in various lesions of the brain were measured in both groups of mice. As a result, corticosterone pretreatment dose-dependently suppressed plasma ACTH response to restraint stress to a significantly lesser extent in GF mice than in SPF mice. GF mice exhibited increased NE and 5-HT levels in the cortex and hippocampus relative to SPF mice, although there was no difference in GABA concentration in any parts of the brain between either group of mice. These results further support the concept that the series of events in the gastrointestinal tract following postnatal microbial colonization can have a long-lasting impact on the neural processing of sensory information regarding the endocrine–stress axis.