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Front. Immunol. | doi: 10.3389/fimmu.2019.02655

Interactions between gut microbiota and acute restraint stress in peripheral structures of the hypothalamic-pituitary-adrenal axis and the intestine of male mice

 Karla Vagnerova1,  Martin Vodicka1,  Petra Hermanova2, Peter Ergang1, Dagmar Srutkova2, Petra Klusonova1, Katerina Balounova1, Tomas Hudcovic2 and  Jiri Pacha1*
  • 1Institute of Physiology (ASCR), Czechia
  • 2Institute of Microbiology (ASCR), Czechia

The gut microbiota play an important role in shaping brain functions and behavior, including the activity of the hypothalamus-pituitary-adrenocortical (HPA) axis. However, little is known about the effect of the microbiota on the distinct structures (hypothalamus, pituitary, adrenals) of the HPA axis. In the present study, we analyzed the influence of the microbiota on acute restraint stress (ARS) response in the pituitary, adrenal gland and intestine, an organ of extra-adrenal glucocorticoid synthesis. Using specific pathogen-free (SPF) and germ-free (GF) male BALB/c mice, we showed that the plasma corticosterone response to ARS was higher in GF than in SPF mice. In the pituitary, stress downregulated the expression of the gene encoding CRH receptor type 1 (Crhr1), upregulated the expression of the Fkbp5 gene regulating glucocorticoid receptor sensitivity and did not affect the expression of the proopiomelanocortin (Pomc) and glucocorticoid receptor (Gr) genes. In contrast, the microbiota downregulated the expression of pituitary Pomc and Crhr1 but had no effect on Fkbp5 and Gr. In the adrenals, the steroidogenic pathway was strongly stimulated by ARS at the level of the steroidogenic transcriptional regulator Sf-1 and cholesterol transporter Star, but the effect of the microbiota on adrenal steroidogenesis was weak and was significantly detected only at the level of gene Cyp11a1, encoding the cholesterol side-chain cleavage enzyme. Unlike adrenal Sf-1, the expression of the gene Lrh-1, which encodes the crucial transcriptional regulator of intestinal steroidogenesis, was modulated by the microbiota and ARS and this effect differed between the ileum and colon. The findings demonstrate that gut microbiota have an impact on the response of the pituitary, adrenals and intestine to ARS and that the interaction between stress and the microbiota during activation of glucocorticoid steroidogenesis differs between organs. The results suggest that downregulated expression of pituitary Pomc and Crhr1 in SPF animals might be an important factor in the exaggerated HPA response of GF mice to

Keywords: acute restraint stress, Gut Microbiota, germ-free, Mice, HPA axis, intestine, extra-adrenal glucocorticoid synthesis

Received: 17 Apr 2019; Accepted: 28 Oct 2019.

Copyright: © 2019 Vagnerova, Vodicka, Hermanova, Ergang, Srutkova, Klusonova, Balounova, Hudcovic and Pacha. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Jiri Pacha, Institute of Physiology (ASCR), Prague, 142 20, Prague, Czechia,