The Gut Microbiota Affects Corticosterone Production in the Murine Small Intestine

• Published in: International journal of molecular sciences 2021-04, Vol.22 (8), p.4229
• Main Authors: Ergang, Peter, Vagnerová, Karla, Hermanová, Petra, Vodička, Martin, Jágr, Michal, Šrůtková, Dagmar, Dvořáček, Václav, Hudcovic, Tomáš, Pácha, Jiří
• Format: Article
• Language: English
• Subjects: 11β-hydroxysteroid dehydrogenase; Adrenal glands; Animal models; anti-CD3 antibody; Antibodies; CD3 antigen; Cholesterol; Corticosterone; Cytokines; Dehydrogenases; Digestive system; Enzymes; extra-adrenal steroidogenesis; Germfree; Glucocorticoids; Hormones; Immunomodulation; Inflammation; Interleukin 1; Interleukin 6; Intestinal microflora; Intestine; Metabolism; Metabolites; microbiome; Microbiota; Microorganisms; Regulation; Small intestine; Specific pathogen free; Steroidogenesis; Steroidogenic acute regulatory protein; Transcription
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22084229

Glucocorticoids (GCs) are hormones that are released in response to stressors and exhibit many activities, including immunomodulatory and anti-inflammatory activities. They are primarily synthesized in the adrenal gland but are also produced in peripheral tissues via regeneration of adrenal 11-oxo metabolites or by synthesis from cholesterol. The present study investigated the influence of the microbiota on steroidogenesis and regeneration of corticosterone in the intestine of germ-free (GF) and specific pathogen-free mice challenged with a physical stressor (anti-CD3 antibody i.p. injection). In the small intestine, acute immune stress resulted in increased mRNA levels of the proinflammatory cytokines , and and genes involved in steroidogenesis ( and ), as well as in regeneration of active GCs from their 11-oxo metabolites ( ). GF mice showed a generally reduced transcriptional response to immune stress, which was accompanied by decreased intestinal corticosterone production and reduced expression of the GC-sensitive marker . In contrast, the interaction between stress and the microbiota was not detected at the level of plasma corticosterone or the transcriptional response of adrenal steroidogenic enzymes. The results indicate a differential immune stress-induced intestinal response to proinflammatory stimuli and local corticosterone production driven by the gut microbiota.