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.
- 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
Gut microbiota provides a wide range of beneficial function for the host and has an immense effect on the host's health state. It has also been shown that gut microbiome is often involved in the biotransformation of xenobiotics; however, the molecular mechanisms of the interaction between the gut bacteria and the metabolism of drugs by the host are still unclear. To investigate the effect of microbial colonization on messenger RNA (mRNA) expression of liver cytochromes P450 (CYPs), the main drug-metabolizing enzymes, we used germ-free (GF) mice, lacking the intestinal flora and mice monocolonized by non-pathogenic bacteria Lactobacillus plantarum NIZO2877 or probiotic bacteria Escherichia coli Nissle 1917 compared to specific pathogen-free (SPF) mice. Our results show that the mRNA expression of Cyp1a2 and Cyp2e1 was significantly increased, while the expression of Cyp3a11 mRNA was decreased under GF conditions compared to the SPF mice. The both bacteria L. plantarum NIZO2877 and E. coli Nissle 1917 given to the GF mice decreased the level of Cyp1a2 mRNA and normalized it to the control level. On the other hand, the colonization by these bacteria had no effect on the expression of Cyp3a11 mRNA in the liver of the GF mice (which remained decreased). Surprisingly, monocolonization with chosen bacterial strains has shown a different effect on the expression of Cyp2e1 mRNA in GF mice. Increased level of Cyp2e1 expression observed in the GF mice was found also in mice colonized by L. plantarum NIZO2877; however, the colonization with probiotic E. coli Nissle 1917 caused a decrease in Cyp2e1 expression and partially restored the SPF mice conditions.
- MeSH
- Escherichia coli genetika růst a vývoj metabolismus MeSH
- gnotobiologické modely MeSH
- játra enzymologie MeSH
- Lactobacillus genetika růst a vývoj metabolismus MeSH
- messenger RNA genetika metabolismus MeSH
- myši inbrední BALB C MeSH
- myši genetika mikrobiologie MeSH
- střevní mikroflóra * MeSH
- systém (enzymů) cytochromů P-450 genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši genetika mikrobiologie MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- ionizující záření MeSH
- mitogeny MeSH
- Nocardia MeSH
- střevní sliznice imunologie účinky záření MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
