Assessment of the Inflammatory Effects of Gut Microbiota from Human Twins Discordant for Ulcerative Colitis on Germ-free Mice

Author:

Knudsen Lina A1,Zachariassen Line SF2,Strube Mikael L3,Havelund Jesper F4,Pilecki Bartosz5,Nexoe Anders B5,Møller Frederik T6,Sørensen Signe B7,Marcussen Niels8,Faergeman Nils J4,Franke Andre9,Bang Corinna9,Holmskov Uffe5,Hansen Axel K10,Andersen Vibeke11

Affiliation:

1. Medical Department, Molecular Diagnostic and Clinical Research, University Hospital of Southern Denmark, Aabenraa, Denmark; IRS-Center Sonderjylland, University of South- ern Denmark, Odense, Denmark

2. Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark

3. DTU Bioengineering, Technical University of Denmark, Lyngby, Denmark

4. VILLUM Center for Bioanalytical Sciences, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark

5. Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark

6. Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark

7. Medical Department, Molecular Diagnostic and Clinical Research, University Hospital of Southern Denmark, Aabenraa, Denmark; Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark

8. Department of Clinical Pathology, Odense University Hospital, Odense, Denmark

9. Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany

10. Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark;, Email: akh@sund.ku.dk

11. Medical Department, Molecular Diagnostic and Clinical Research, University Hospital of Southern Denmark, Aabenraa, Denmark; IRS-Center Sonderjylland, University of Southern Denmark, Odense, Denmark; Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark

Abstract

Disturbances in gut microbiota are prevalent in inflammatory bowel disease (IBD), which includes ulcerative colitis (UC). However, whether these disturbances contribute to development of the disease or are a result of the disease is unclear. In pairs of human twins discordant for IBD, the healthy twin has a higher risk of developing IBD and a gut microbiota that is more similar to that of IBD patients as compared with healthy individuals. Furthermore, appropriate medical treatment may mitigate these disturbances. To study the correlation between microbiota and IBD, we transferred stool samples from a discordant human twin pair: one twin being healthy and the other receiving treatment for UC. The stool samples were transferred from the disease-discordant twins to germ-free pregnant dams. Colitis was induced in the offspring using dextran sodium sulfate. As compared with offspring born to mice dams inoculated with stool from the healthy cotwin, offspring born to dams inoculated with stool from the UC-afflicted twin had a lower disease activity index, less gut inflammation, and a microbiota characterized by higher α diversity and a more antiinflammatory profile that included the presence and higher abundance of antiinflammatory species such as Akkermansia spp., Bacteroides spp., and Parabacteroides spp. These findings suggest that the microbiota from the healthy twin may have had greater inflammatory properties than did that of the twin undergoing UC treatment.

Publisher

American Association for Laboratory Animal Science

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