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

Sajad Moshkelgosha, Giulia Masetti, Utta Berchner-Pfannschmidt, Hedda Luise Verhasselt, Mareike Horstmann, Salvador Diaz-Cano, Alistair Noble, Barbel Edelman, Danila Covelli, Sue Plummer, Julian R Marchesi, Marian Ludgate, Filippo Biscarini, Anja Eckstein, J Paul Banga

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)932-941
Number of pages10
JournalHormone and Metabolic Research
Volume50
Issue number12
DOIs
Publication statusPublished - Dec 2018

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    Moshkelgosha, S., Masetti, G., Berchner-Pfannschmidt, U., Verhasselt, H. L., Horstmann, M., Diaz-Cano, S., Noble, A., Edelman, B., Covelli, D., Plummer, S., Marchesi, J. R., Ludgate, M., Biscarini, F., Eckstein, A., & Banga, J. P. (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), 932-941. https://doi.org/10.1055/a-0653-3766