Microbiota modulates the steroid response to acute immune stress in male mice.

Microbiota plays a role in shaping the HPA-axis response to psychological stressors. To examine the role of microbiota in response to acute immune stressor, we stimulated the adaptive immune system by anti-CD3 antibody injection and investigated the expression of adrenal steroidogenic enzymes and profiling of plasma corticosteroids and their metabolites in specific pathogen-free (SPF) and germ-free (GF) mice. Using UHPLC-MS/MS, we showed that 4 hours after immune challenge the plasma levels of pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone (CORT), 11-dehydroCORT and their 3α/β-, 5α-, and 20α-reduced metabolites were increased in SPF mice, but in their GF counterparts, only CORT was increased. Neither immune stress nor microbiota changed the mRNA and protein levels of enzymes of adrenal steroidogenesis. In contrast, immune stress resulted in downregulated expression of steroidogenic genes ( Star , Cyp11a1 , Hsd3b1 , Hsd3b6 ) and upregulated expression of genes of the 3α-hydroxysteroid oxidoreductase pathway ( Akr1c21 , Dhrs9 ) in the testes of SPF mice. In the liver, immune stress downregulated the expression of genes encoding enzymes with 3β-hydroxysteroid dehydrogenase (HSD) ( Hsd3b2 , Hsd3b3 , Hsd3b4 , Hsd3b5 ), 3α-HSD ( Akr1c14 ), 20α-HSD ( Akr1c6 , Hsd17b1 , Hsd17b2 ) and 5α-reductase ( Srd5a1 ) activities, except for Dhrs9 , which was upregulated. In the colon, microbiota downregulated Cyp11a1 and modulated the response of Hsd11b1 and Hsd11b2 expression to immune stress. These data underline the role of microbiota in shaping the response to immune stressor. Microbiota modulates the stress-induced increase in C ₂₁ steroids, including those that are neuroactive that could play a role in alteration of HPA axis response to stress in GF animals.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Vagnerová, Gazárková, Vodička, Ergang, Klusoňová, Hudcovic, Šrůtková, Petr Hermanová, Nováková and Pácha.)