Wednesday, July 15, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Franziska Schmidt
,
Charité - Universitätsmedizin Berlin, Department of Gastroenterology, Infectiology and Rheumatology, Berlin, Germany
Tassilo Kruis, MD
,
Charité - Universitätsmedizin Berlin, Department of Gastroenterology, Infectiology and Rheumatology, Berlin, Germany
Arvind Batra, PhD
,
Charité - Universitätsmedizin Berlin, Department of Gastroenterology, Infectiology and Rheumatology, Berlin, Germany
Gunnar Loh, VMD
,
German Institute of Human Nutrition Potsdam-Rehbrücke, Department of Gastrointestinal Microbiology, Nuthetal, Germany
Michael Schumann, MD
,
Charité - Universitätsmedizin Berlin, Department of Gastroenterology, Infectiology and Rheumatology, Berlin, Germany
Anja Kuehl, PhD
,
Charité - Universitätsmedizin Berlin, Department of Gastroenterology, Infectiology and Rheumatology, Berlin, Germany
Michael Blaut, PhD
,
German Institute of Human Nutrition Potsdam-Rehbrücke, Department of Gastrointestinal Microbiology, Nuthetal, Germany
Britta Siegmund, MD
,
Charité - Universitätsmedizin Berlin, Department of Gastroenterology, Infectiology and Rheumatology, Berlin, Germany
To understand the consequence of intestinal microbiota for epithelial integrity and immune cell homeostasis we assessed the immune cell phenotype in the gut of germfree (GF), specific pathogen free (SPF) mice and GF-mice colonized at age of 5 weeks with SPF-microbiota (COL) in health and intestinal inflammation.
The phenotype of lamina propria mononuclear cells was characterized by flow cytometry and immunohistology. Colitis was induced by dextran sodium sulfate (DSS). Barrier function of the colon was analyzed by electrophysiology.
In the ileum of GF-mice macrophages were increased with the pro-inflammatory CD11c+ and MHCII+ subset dominating, whereas, the number of T-cells was profoundly decreased. In parallel, in GF-mice the total colonic epithelial resistance was decreased accompanied by increased 3H-mannitol- and decreased HRP-flux suggesting a barrier dysfunction. By exposing these mice to DSS at week 9 of age, an additional barrier-disturbing factor was introduced. GF-mice were significantly more susceptible to DSS than SPF- or COL-mice as indicated by higher mortality, hence indicating that the exposure to the microbiota forms a prerequisite to develop epithelial integrity. However, the inflammation score was higher in SPF- than in COL-mice.
In conclusion, the microbiota is essential for the development of the colonic integrity and local immune cell composition. Future studies will serve to determine i) the window of opportunity for the microbiota to exert these beneficial effects, and ii) the optimal microbiota composition.
