Z Gastroenterol 2019; 57(05): e137-e138
DOI: 10.1055/s-0039-1691870
POSTER
CED
Georg Thieme Verlag KG Stuttgart · New York

Does the gut microbiome affect intestinal steroidogenesis?

M Krainer
1   Department of Internal Medicine, Research Unit for Translational Nuclear Receptor Research, Division of Gastroenterology and Hepatology, Medical University Graz, Graz, Austria
,
J Sommer
1   Department of Internal Medicine, Research Unit for Translational Nuclear Receptor Research, Division of Gastroenterology and Hepatology, Medical University Graz, Graz, Austria
,
D Silbert-Wagner
1   Department of Internal Medicine, Research Unit for Translational Nuclear Receptor Research, Division of Gastroenterology and Hepatology, Medical University Graz, Graz, Austria
,
S Racedo
1   Department of Internal Medicine, Research Unit for Translational Nuclear Receptor Research, Division of Gastroenterology and Hepatology, Medical University Graz, Graz, Austria
,
K Panzitt
1   Department of Internal Medicine, Research Unit for Translational Nuclear Receptor Research, Division of Gastroenterology and Hepatology, Medical University Graz, Graz, Austria
,
M Wagner
1   Department of Internal Medicine, Research Unit for Translational Nuclear Receptor Research, Division of Gastroenterology and Hepatology, Medical University Graz, Graz, Austria
› Author Affiliations
Further Information

Publication History

Publication Date:
16 May 2019 (online)

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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) and transcription factor LRH-1. Both, steroidogenic enzymes as well as the regulating NR LRH-1 are 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 each). 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 expressed in germfree mice. On mRNA levels the most robust changes were detected for Hsd3b1 and 3, 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/conclusion:

The presence of a 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. Future studies will determine the expression levels in patients before and after FMT to translate the rodent findings into a clinically relevant background in human patients.