Imperial College London
Alternate

ProfessorJulianMarchesi

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Digestive Health
 
 
 
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Contact

 

+44 (0)20 3312 6197j.marchesi

 
 
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Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Moshkelgosha:2021:10.1186/s40168-020-00952-4,
author = {Moshkelgosha, S and Verhasselt, HL and Masetti, G and Covelli, D and Biscarini, F and Horstmann, M and Daser, A and Westendorf, AM and Jesenek, C and Philipp, S and Diaz-Cano, S and Banga, JP and Michael, D and Plummer, S and Marchesi, JR and Eckstein, A and Ludgate, M and Berchner-Pfannschmidt, U and INDIGO, consortium},
doi = {10.1186/s40168-020-00952-4},
journal = {Microbiome},
title = {Modulating gut microbiota in a mouse model of Graves' orbitopathy and its impact on induced disease},
url = {http://dx.doi.org/10.1186/s40168-020-00952-4},
volume = {9},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Graves' disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves' orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks). RESULTS: In ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology. Firmicutes were increased, and Bacteroidetes reduced relative to ddH2O-βgal; CCL5 was increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively with Akkermansia spp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors' microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore
AU  - Moshkelgosha,S
AU  - Verhasselt,HL
AU  - Masetti,G
AU  - Covelli,D
AU  - Biscarini,F
AU  - Horstmann,M
AU  - Daser,A
AU  - Westendorf,AM
AU  - Jesenek,C
AU  - Philipp,S
AU  - Diaz-Cano,S
AU  - Banga,JP
AU  - Michael,D
AU  - Plummer,S
AU  - Marchesi,JR
AU  - Eckstein,A
AU  - Ludgate,M
AU  - Berchner-Pfannschmidt,U
AU  - INDIGO,consortium
DO  - 10.1186/s40168-020-00952-4
PY  - 2021///
SN  - 2049-2618
TI  - Modulating gut microbiota in a mouse model of Graves' orbitopathy and its impact on induced disease
T2  - Microbiome
UR  - http://dx.doi.org/10.1186/s40168-020-00952-4
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33593429
UR  - http://hdl.handle.net/10044/1/91385
VL  - 9
ER  -
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