Gut Microbiome Associated With Graves Disease and Graves Orbitopathy: The INDIGO Multicenter European Study.

Autor:	Biscarini F; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XW, UK.; Department of Bioinformatics, Parco Tecnologico Padano Srl (PTP), Lodi, 26900, Italy.; Institute of Agricultural Biology and Biotechnology, Italian National Research Council (CNR), Milan, 20133, Italy., Masetti G; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XW, UK.; Department of Bioinformatics, Parco Tecnologico Padano Srl (PTP), Lodi, 26900, Italy., Muller I; Department of Clinical Sciences and Community Health, University of Milan, Milan, 35-I-20122, Italy.; Graves' Orbitopathy Center, Endocrinology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan, Milan, 35-I-20122, Italy., Verhasselt HL; Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, 45147, Germany.; Cultech Ltd., Baglan, Port Talbot, SA12 7BZ, UK., Covelli D; Department of Bioinformatics, Parco Tecnologico Padano Srl (PTP), Lodi, 26900, Italy.; Graves' Orbitopathy Center, Endocrinology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan, Milan, 35-I-20122, Italy.; Cultech Ltd., Baglan, Port Talbot, SA12 7BZ, UK., Colucci G; Graves' Orbitopathy Center, Endocrinology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan, Milan, 35-I-20122, Italy., Zhang L; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XW, UK.; Centre for Stem Cell Biology, School of Biosciences, University of Sheffield, Sheffield, S10 2TN, UK., Draman MS; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XW, UK.; KPJ Healthcare University College, Kota Seriemas, 71800 Nilai, Negeri Sembilan, Malaysia., Okosieme O; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XW, UK., Taylor P; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XW, UK., Daumerie C; Department of Endocrinology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, B-1200, Belgium., Burlacu MC; Department of Endocrinology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, B-1200, Belgium., Marinò M; Department of Endocrinology, University Hospital of Pisa, Pisa, 56124, Italy.; Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa, Pisa, 56124, Italy., Ezra DG; Moorfields Eye Hospital NIHR Biomedical Research Centre for Ophthalmology, London and UCL Institute of Ophthalmology, London, EC4 9EL, UK., Perros P; Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK., Plummer S; Cultech Ltd., Baglan, Port Talbot, SA12 7BZ, UK., Eckstein A; Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Essen, 45147, Germany., Salvi M; Graves' Orbitopathy Center, Endocrinology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan, Milan, 35-I-20122, Italy., Marchesi JR; Microbiomes, Microbes and Informatics Group, School of Biosciences, Cardiff University, Cardiff, CF10 3AX, UK.; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, W2 1NY, UK., Ludgate M; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XW, UK.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2023 Jul 14; Vol. 108 (8), pp. 2065-2077.
DOI:	10.1210/clinem/dgad030
Abstrakt:	Context: Gut bacteria can influence host immune responses but little is known about their role in tolerance-loss mechanisms in Graves disease (GD; hyperthyroidism caused by autoantibodies, TRAb, to the thyrotropin receptor, TSHR) and its progression to Graves orbitopathy (GO). Objective: This work aimed to compare the fecal microbiota in GD patients, with GO of varying severity, and healthy controls (HCs). Methods: Patients were recruited from 4 European countries (105 GD patients, 41 HCs) for an observational study with cross-sectional and longitudinal components. Results: At recruitment, when patients were hyperthyroid and TRAb positive, Actinobacteria were significantly increased and Bacteroidetes significantly decreased in GD/GO compared with HCs. The Firmicutes to Bacteroidetes (F:B) ratio was significantly higher in GD/GO than in HCs. Differential abundance of 15 genera was observed in patients, being most skewed in mild GO. Bacteroides displayed positive and negative correlations with TSH and free thyroxine, respectively, and was also significantly associated with smoking in GO; smoking is a risk factor for GO but not GD. Longitudinal analyses revealed that the presence of certain bacteria (Clostridiales) at diagnosis correlated with the persistence of TRAb more than 200 days after commencing antithyroid drug treatment. Conclusion: The increased F:B ratio observed in GD/GO mirrors our finding in a murine model comparing TSHR-immunized with control mice. We defined a microbiome signature and identified changes associated with autoimmunity as distinct from those due to hyperthyroidism. Persistence of TRAb is predictive of relapse; identification of these patients at diagnosis, via their microbiome, could improve management with potential to eradicate Clostridiales. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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