The commensal microbiota affects brain functioning, emotional behavior and ACTH and corticosterone responses to acute stress. However, little is known about the role of the microbiota in shaping the chronic stress response in the peripheral components of the hypothalamus-pituitary-adrenocortical (HPA) axis and in the colon. Here, we studied the effects of the chronic stress-microbiota interaction on HPA axis activity and on the expression of colonic corticotropin-releasing hormone (CRH) system, cytokines and 11β-hydroxysteroid dehydrogenase type 1 (11HSD1), an enzyme that determines locally produced glucocorticoids. Using specific pathogen-free (SPF) and germ-free (GF) BALB/c mice, we showed that the microbiota modulates emotional behavior in social conflicts and the response of the HPA axis, colon and mesenteric lymph nodes (MLN) to chronic psychosocial stress. In the pituitary gland, microbiota attenuated the expression of Fkbp5, a gene regulating glucocorticoid receptor sensitivity, while in the adrenal gland, it attenuated the expression of genes encoding steroidogenesis (MC2R, StaR, Cyp11a1) and catecholamine synthesis (TH, PNMT). The pituitary expression of CRH receptor type 1 (CRHR1) and of proopiomelanocortin was not influenced by microbiota. In the colon, the microbiota attenuated the expression of 11HSD1, CRH, urocortin UCN2 and its receptor, CRHR2, but potentiated the expression of cytokines TNFα, IFNγ, IL-4, IL-5, IL-6, IL-10, IL-13 and IL-17, with the exception of IL-1β. Compared to GF mice, chronic stress upregulated in SPF animals the expression of pituitary Fkbp5 and colonic CRH and UCN2 and downregulated the expression of colonic cytokines. Differences in the stress responses of both GF and SPF animals were also observed when immunophenotype of MLN cells and their secretion of cytokines were analyzed. The data suggest that the presence of microbiota/intestinal commensals plays an important role in shaping the response of peripheral tissues to stress and indicates possible pathways by which the environment can interact with glucocorticoid signaling.

• Klíčová slova
• 11β-hydroxysteroid dehydrogenase, Adrenal gland, CRH system, Chronic psychosocial stress, Colon, Cytokines, Immune system, Local metabolism of glucocorticoids, Mice, Microbiome,
• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 metabolismus   MeSH
• adrenokortikotropní hormon metabolismus   MeSH
• chování zvířat fyziologie   MeSH
• cytokiny metabolismus   MeSH
• exprese genu fyziologie   MeSH
• glukokortikoidy genetika   fyziologie   MeSH
• hormon uvolňující kortikotropin metabolismus   MeSH
• hypofýza MeSH
• kortikosteron metabolismus   MeSH
• mikrobiota fyziologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nadledviny MeSH
• psychický stres genetika   metabolismus   MeSH
• psychologie MeSH
• receptory glukokortikoidů metabolismus   MeSH
• regulace genové exprese fyziologie   MeSH
• sociální chování MeSH
• systém hypofýza - nadledviny mikrobiologie   MeSH
• systém hypotalamus-hypofýza mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
• adrenokortikotropní hormon MeSH
• cytokiny MeSH
• glukokortikoidy MeSH
• hormon uvolňující kortikotropin MeSH
• kortikosteron MeSH
• receptory glukokortikoidů MeSH