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Gut microbiome in BALB/c and C57BL/6J mice undergoing experimental thyroid autoimmunity associate with differences in immunological responses and thyroid function

Moshkelgosha, Sajad, Masetti, Giulia, Berchner-Pfannschmidt, Utta, Verhasselt, Hedda, Horstmann, Mareike, Diaz-Cano, Salvador, Noble, Alistair, Edelman, Barbel, Covelli, Danila, Plummer, Sue, Marchesi, Julian, Ludgate, Marian, Biscarini, Filippo, Eckstein, Anja and Banga, J. 2018. Gut microbiome in BALB/c and C57BL/6J mice undergoing experimental thyroid autoimmunity associate with differences in immunological responses and thyroid function. Hormone and Metabolic Research 50 (12) , pp. 932-941. 10.1055/a-0653-3766

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Thieme Publishing / Georg Thieme Verlag
ISSN: 0018-5043
Date of First Compliant Deposit: 29 August 2018
Date of Acceptance: 26 June 2018
Last Modified: 14 Aug 2019 02:05

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