Gut microbiota in experimental murine model of Graves’ orbitopathy established in different environments may modulate clinical presentation of disease
Abstract Background Variation in induced models of autoimmunity has been attributed to the housing environment and its effect on the gut microbiota. In Graves’ disease (GD), autoantibodies to the thyrotropin receptor (TSHR) cause autoimmune hyperthyroidism. Many GD patients develop Graves’ orbitopat...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Microbiome |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40168-018-0478-4 |
| _version_ | 1818966533138808832 |
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| author | Giulia Masetti Sajad Moshkelgosha Hedda-Luise Köhling Danila Covelli Jasvinder Paul Banga Utta Berchner-Pfannschmidt Mareike Horstmann Salvador Diaz-Cano Gina-Eva Goertz Sue Plummer Anja Eckstein Marian Ludgate Filippo Biscarini Julian Roberto Marchesi the INDIGO consortium |
| author_facet | Giulia Masetti Sajad Moshkelgosha Hedda-Luise Köhling Danila Covelli Jasvinder Paul Banga Utta Berchner-Pfannschmidt Mareike Horstmann Salvador Diaz-Cano Gina-Eva Goertz Sue Plummer Anja Eckstein Marian Ludgate Filippo Biscarini Julian Roberto Marchesi the INDIGO consortium |
| author_sort | Giulia Masetti |
| collection | DOAJ |
| description | Abstract Background Variation in induced models of autoimmunity has been attributed to the housing environment and its effect on the gut microbiota. In Graves’ disease (GD), autoantibodies to the thyrotropin receptor (TSHR) cause autoimmune hyperthyroidism. Many GD patients develop Graves’ orbitopathy or ophthalmopathy (GO) characterized by orbital tissue remodeling including adipogenesis. Murine models of GD/GO would help delineate pathogenetic mechanisms, and although several have been reported, most lack reproducibility. A model comprising immunization of female BALBc mice with a TSHR expression plasmid using in vivo electroporation was reproduced in two independent laboratories. Similar orbital disease was induced in both centers, but differences were apparent (e.g., hyperthyroidism in Center 1 but not Center 2). We hypothesized a role for the gut microbiota influencing the outcome and reproducibility of induced GO. Results We combined metataxonomics (16S rRNA gene sequencing) and traditional microbial culture of the intestinal contents from the GO murine model, to analyze the gut microbiota in the two centers. We observed significant differences in alpha and beta diversity and in the taxonomic profiles, e.g., operational taxonomic units (OTUs) from the genus Lactobacillus were more abundant in Center 2, and Bacteroides and Bifidobacterium counts were more abundant in Center 1 where we also observed a negative correlation between the OTUs of the genus Intestinimonas and TSHR autoantibodies. Traditional microbiology largely confirmed the metataxonomics data and indicated significantly higher yeast counts in Center 1 TSHR-immunized mice. We also compared the gut microbiota between immunization groups within Center 2, comprising the TSHR- or βgal control-immunized mice and naïve untreated mice. We observed a shift of the TSHR-immunized mice bacterial communities described by the beta diversity weighted Unifrac. Furthermore, we observed a significant positive correlation between the presence of Firmicutes and orbital-adipogenesis specifically in TSHR-immunized mice. Conclusions The significant differences observed in microbiota composition from BALBc mice undergoing the same immunization protocol in comparable specific-pathogen-free (SPF) units in different centers support a role for the gut microbiota in modulating the induced response. The gut microbiota might also contribute to the heterogeneity of induced response since we report potential disease-associated microbial taxonomies and correlation with ocular disease. |
| first_indexed | 2024-12-20T13:34:25Z |
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| id | doaj.art-5c989b25ca984a3dac9fe189f5e70b89 |
| institution | Directory Open Access Journal |
| issn | 2049-2618 |
| language | English |
| last_indexed | 2024-12-20T13:34:25Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbiome |
| spelling | doaj.art-5c989b25ca984a3dac9fe189f5e70b892022-12-21T19:39:01ZengBMCMicrobiome2049-26182018-05-016111510.1186/s40168-018-0478-4Gut microbiota in experimental murine model of Graves’ orbitopathy established in different environments may modulate clinical presentation of diseaseGiulia Masetti0Sajad Moshkelgosha1Hedda-Luise Köhling2Danila Covelli3Jasvinder Paul Banga4Utta Berchner-Pfannschmidt5Mareike Horstmann6Salvador Diaz-Cano7Gina-Eva Goertz8Sue Plummer9Anja Eckstein10Marian Ludgate11Filippo Biscarini12Julian Roberto Marchesi13the INDIGO consortium14Division of Infection & Immunity, School of Medicine, Cardiff UniversityMolecular Ophthalmology, Department of Ophthalmology, University Hospital Essen/University of Duisburg-EssenCultech Ltd.Cultech Ltd.Molecular Ophthalmology, Department of Ophthalmology, University Hospital Essen/University of Duisburg-EssenMolecular Ophthalmology, Department of Ophthalmology, University Hospital Essen/University of Duisburg-EssenMolecular Ophthalmology, Department of Ophthalmology, University Hospital Essen/University of Duisburg-EssenKing’s College Hospital NHS Foundation Trust (SDC)Molecular Ophthalmology, Department of Ophthalmology, University Hospital Essen/University of Duisburg-EssenCultech Ltd.Molecular Ophthalmology, Department of Ophthalmology, University Hospital Essen/University of Duisburg-EssenDivision of Infection & Immunity, School of Medicine, Cardiff UniversityDivision of Infection & Immunity, School of Medicine, Cardiff UniversitySchool of Biosciences, Cardiff UniversityINDIGO ConsortiumAbstract Background Variation in induced models of autoimmunity has been attributed to the housing environment and its effect on the gut microbiota. In Graves’ disease (GD), autoantibodies to the thyrotropin receptor (TSHR) cause autoimmune hyperthyroidism. Many GD patients develop Graves’ orbitopathy or ophthalmopathy (GO) characterized by orbital tissue remodeling including adipogenesis. Murine models of GD/GO would help delineate pathogenetic mechanisms, and although several have been reported, most lack reproducibility. A model comprising immunization of female BALBc mice with a TSHR expression plasmid using in vivo electroporation was reproduced in two independent laboratories. Similar orbital disease was induced in both centers, but differences were apparent (e.g., hyperthyroidism in Center 1 but not Center 2). We hypothesized a role for the gut microbiota influencing the outcome and reproducibility of induced GO. Results We combined metataxonomics (16S rRNA gene sequencing) and traditional microbial culture of the intestinal contents from the GO murine model, to analyze the gut microbiota in the two centers. We observed significant differences in alpha and beta diversity and in the taxonomic profiles, e.g., operational taxonomic units (OTUs) from the genus Lactobacillus were more abundant in Center 2, and Bacteroides and Bifidobacterium counts were more abundant in Center 1 where we also observed a negative correlation between the OTUs of the genus Intestinimonas and TSHR autoantibodies. Traditional microbiology largely confirmed the metataxonomics data and indicated significantly higher yeast counts in Center 1 TSHR-immunized mice. We also compared the gut microbiota between immunization groups within Center 2, comprising the TSHR- or βgal control-immunized mice and naïve untreated mice. We observed a shift of the TSHR-immunized mice bacterial communities described by the beta diversity weighted Unifrac. Furthermore, we observed a significant positive correlation between the presence of Firmicutes and orbital-adipogenesis specifically in TSHR-immunized mice. Conclusions The significant differences observed in microbiota composition from BALBc mice undergoing the same immunization protocol in comparable specific-pathogen-free (SPF) units in different centers support a role for the gut microbiota in modulating the induced response. The gut microbiota might also contribute to the heterogeneity of induced response since we report potential disease-associated microbial taxonomies and correlation with ocular disease.http://link.springer.com/article/10.1186/s40168-018-0478-4Graves’ orbitopathyGraves’ diseaseInduced animal modelGut microbiotaTSHRMetataxonomics |
| spellingShingle | Giulia Masetti Sajad Moshkelgosha Hedda-Luise Köhling Danila Covelli Jasvinder Paul Banga Utta Berchner-Pfannschmidt Mareike Horstmann Salvador Diaz-Cano Gina-Eva Goertz Sue Plummer Anja Eckstein Marian Ludgate Filippo Biscarini Julian Roberto Marchesi the INDIGO consortium Gut microbiota in experimental murine model of Graves’ orbitopathy established in different environments may modulate clinical presentation of disease Microbiome Graves’ orbitopathy Graves’ disease Induced animal model Gut microbiota TSHR Metataxonomics |
| title | Gut microbiota in experimental murine model of Graves’ orbitopathy established in different environments may modulate clinical presentation of disease |
| title_full | Gut microbiota in experimental murine model of Graves’ orbitopathy established in different environments may modulate clinical presentation of disease |
| title_fullStr | Gut microbiota in experimental murine model of Graves’ orbitopathy established in different environments may modulate clinical presentation of disease |
| title_full_unstemmed | Gut microbiota in experimental murine model of Graves’ orbitopathy established in different environments may modulate clinical presentation of disease |
| title_short | Gut microbiota in experimental murine model of Graves’ orbitopathy established in different environments may modulate clinical presentation of disease |
| title_sort | gut microbiota in experimental murine model of graves orbitopathy established in different environments may modulate clinical presentation of disease |
| topic | Graves’ orbitopathy Graves’ disease Induced animal model Gut microbiota TSHR Metataxonomics |
| url | http://link.springer.com/article/10.1186/s40168-018-0478-4 |
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