Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Krainer, M.
Does the Microbiome Affect Intestinal Steroidogenesis?
Humanmedizin; [ Diplomarbeit ] Medical University of Graz; 2020. pp. 58
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Panzitt Katrin
- Wagner Martin
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- Abstract:
- Introduction: The intestine is a source of locally active glucocorticoid generation, which is relevant for the maintenance of intestinal immune homeostasis. Steroidogenic enzymes in the intestine are regulated by the nuclear receptor (NR) LRH-1. The expression of both, steroidogenic enzymes as well as the regulating NR LRH-1 is reduced in inflamed parts of the colon of patients with inflammatory bowel disease (IBD). Fecal microbiota transplantation is a promising experimental therapeutic option for IBD patients with ulcerative colitis. We therefore hypothesize, that the gut microbiome may affect local steroidogenesis. Methods: To determine the effect of the microbiome on intestinal steroidogenesis, we compared different parts of the intestine (jejunum, ileum, and colon) of germfree and conventional mice (n=5 per group). We focused on the key steroidogenic enzymes Cyp11a1, Cyp11b1 and Hsd3b, which are all regulated by LRH-1. To test expression levels, we performed RT-qPCR, Western Blotting (WB) and immunofluorescence (IF) staining. Results: Differences were most pronounced on protein levels for Cyp11a1 and Cyp11b1, which were significantly lower in germfree mice. On mRNA levels the most robust changes were detected for Hsd3b1 and Hsd3b3, which were expressed significantly less in the colon of germfree mice contrary to increased expression in the ileum of germfree mice. IF showed lower expression of Cyp11b1 in the colon of germfree mice. Discussion: The presence of the gut microbiome significantly affects steroidogenic enzyme expression in the intestine. Cyp11a1 and Cyp11b1 are significantly less expressed in germfree mice. The role of LRH-1 in mediating these effects is currently not clear and further in-depth analysis (e.g. LRH-1 chromatin immunoprecipitations) is required.