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Horm Metab Res 2018; 50(12): 932-941
DOI: 10.1055/a-0653-3766
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Gut Microbiome in BALB/c and C57BL/6J Mice Undergoing Experimental Thyroid Autoimmunity Associate with Differences in Immunological Responses and Thyroid Function

Sajad Moshkelgosha   *
1   Faculty of Life Sciences & Medicine, King’s College London, London, UK
2   Molecular Ophthalmology, Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany
3   Present address: Latner Thoracic Surgery Research Laboratories, University Health Network (UHN), Toronto, Canada
,
Giulia Masetti   *
4   Departments of Bioinformatics, PTP Science Park, via Einstein loc. Cascina Codazza, Lodi, Italy
5   Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, UK
,
Utta Berchner-Pfannschmidt
2   Molecular Ophthalmology, Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany
,
Hedda Luise Verhasselt
6   Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
,
Mareike Horstmann
2   Molecular Ophthalmology, Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany
,
Salvador Diaz-Cano
7   King’s College Hospital NHS Foundation Trust, Department of Histopathology, London, UK
,
Alistair Noble
8   Present address: Antigen Presentation Research Group, Imperial College London, Harrow, UK
,
Barbel Edelman
2   Molecular Ophthalmology, Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany
,
Danila Covelli
9   Graves’ Orbitopathy Centre, Department of Clinical Sciences and Community Health, Fondazione Ca’Granda IRCCS, University of Milan, Milan, Italy
,
Sue Plummer
10   Cultech Ltd., Baglan, Port Talbot, UK
,
Julian R. Marchesi
11   School of Biosciences, Cardiff University, Cardiff and Centre for Digestive and Gut Health, Imperial College London, London, UK
,
Marian Ludgate
12   Division of Infection & Immunity, Cardiff University, Cardiff, UK
,
Filippo Biscarini
12   Division of Infection & Immunity, Cardiff University, Cardiff, UK
13   Italian National Council for Research (CNR), Milan, Italy and INDIGO Consortium http://www.indigo-iapp.eu
,
Anja Eckstein
2   Molecular Ophthalmology, Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany
,
J. Paul Banga
1   Faculty of Life Sciences & Medicine, King’s College London, London, UK
2   Molecular Ophthalmology, Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany
› Author Affiliations
Further Information

Publication History

received 07 May 2018

accepted 26 June 2018

Publication Date:
14 August 2018 (online)

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Abstract

Experimental models of hyperthyroid Graves’ disease (GD) and Graves’ orbitopathy (GO) are efficiently developed by genetic immunisation by electroporation with human thyrotropin hormone receptor (hTSHR) A-subunit plasmid in female BALB/c (H-2d) mice. We investigated susceptibility in C57BL/6 J (H-2b) animals to allow studies on disease mechanisms in transgenic and immune response gene knock-out mice. Higher numbers of female C57BL/6 J were positive for pathogenic thyroid stimulating antibodies, but induced hyperthyroidism remained at a low frequency compared to BALB/c animals. Assessment of hTSHR specific T cells showed reduced proliferation in C57BL/6 J animals accompanied with anti-inflammatory IL-10, with less pro-inflammatory IFN-γ compared to BALB/c. Whilst the orbital tissue from immune BALB/c mice showed inflammation and adipogenesis, in contrast C57BL/6 J animals showed normal pathology. We characterised the gut microbiota using 16 S ribosomal RNA gene sequencing to explore its possible pathogenic role in the model. Despite being housed under identical conditions, we observed significantly different organisation of the microbiota (beta-diversity) in the two strains. Taxonomic differences were also noted, with C57BL/6 J showing an enrichment of Operational Taxonomic Units (OTUs) belonging to the Paludibacter and Allobaculum, followed by Limibacter, Anaerophaga and Ureaplasma genera. A higher number of genera significantly correlating with clinical features was observed in C57BL/6 J compared to BALB/c; for example, Limibacter OTUs correlated negatively with thyroid-stimulating antibodies in C57BL/6 J mice. Thus, our data suggest gut microbiota may play a pivotal immunomodulatory role that differentiates the thyroid function and orbital pathology outcome in these two inbred strains undergoing experimental GO.

Key words

Graves’ disease - autoimmunity - TSH-receptor antibodies

* Shared first authorship


Supplementary Material

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