Microbiota affects the expression of genes involved in HPA axis regulation and local metabolism of glucocorticoids in chronic psychosocial stress
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
29990567
DOI
10.1016/j.bbi.2018.07.007
PII: S0889-1591(18)30314-3
Knihovny.cz E-resources
- Keywords
- 11β-hydroxysteroid dehydrogenase, Adrenal gland, CRH system, Chronic psychosocial stress, Colon, Cytokines, Immune system, Local metabolism of glucocorticoids, Mice, Microbiome,
- MeSH
- 11-beta-Hydroxysteroid Dehydrogenase Type 1 metabolism MeSH
- Adrenocorticotropic Hormone metabolism MeSH
- Behavior, Animal physiology MeSH
- Cytokines metabolism MeSH
- Gene Expression physiology MeSH
- Glucocorticoids genetics physiology MeSH
- Corticotropin-Releasing Hormone metabolism MeSH
- Pituitary Gland MeSH
- Corticosterone metabolism MeSH
- Microbiota physiology MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Adrenal Glands MeSH
- Stress, Psychological genetics metabolism MeSH
- Psychology MeSH
- Receptors, Glucocorticoid metabolism MeSH
- Gene Expression Regulation physiology MeSH
- Social Behavior MeSH
- Pituitary-Adrenal System microbiology MeSH
- Hypothalamo-Hypophyseal System microbiology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 11-beta-Hydroxysteroid Dehydrogenase Type 1 MeSH
- Adrenocorticotropic Hormone MeSH
- Cytokines MeSH
- Glucocorticoids MeSH
- Corticotropin-Releasing Hormone MeSH
- Corticosterone MeSH
- Receptors, Glucocorticoid MeSH
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.
Institute of Microbiology of the Czech Academy of Sciences Nový Hrádek Czech Republic
Institute of Physiology Academy of Sciences of the Czech Republic Prague Czech Republic
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