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Atopobium and Fusobacterium as novel candidates for sarcoidosis-associated microbiota

Alexandra Zimmermann, Henrik Knecht, Robert Häsler, Gernot Zissel, Karoline I. Gaede, Sylvia Hofmann, Almut Nebel, Joachim Müller-Quernheim, Stefan Schreiber, Annegret Fischer
European Respiratory Journal 2017 50: 1600746; DOI: 10.1183/13993003.00746-2016
Alexandra Zimmermann
1Institute of Clinical Molecular Biology, Kiel University and University Hospital Schleswig-Holstein, Kiel, Germany
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Henrik Knecht
1Institute of Clinical Molecular Biology, Kiel University and University Hospital Schleswig-Holstein, Kiel, Germany
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Robert Häsler
1Institute of Clinical Molecular Biology, Kiel University and University Hospital Schleswig-Holstein, Kiel, Germany
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Gernot Zissel
2Dept of Pneumology, University of Freiburg, Freiburg, Germany
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Karoline I. Gaede
3BioMaterialBank Nord, Dept of Medicine, Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany
4Airway Research Center North, Member of the German Center for Lung Research
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Sylvia Hofmann
5Dept of Conservation Biology, Helmholtz Centre for Environmental Research, Leipzig, Germany
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Almut Nebel
1Institute of Clinical Molecular Biology, Kiel University and University Hospital Schleswig-Holstein, Kiel, Germany
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Joachim Müller-Quernheim
2Dept of Pneumology, University of Freiburg, Freiburg, Germany
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Stefan Schreiber
1Institute of Clinical Molecular Biology, Kiel University and University Hospital Schleswig-Holstein, Kiel, Germany
6Clinic of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany
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Annegret Fischer
1Institute of Clinical Molecular Biology, Kiel University and University Hospital Schleswig-Holstein, Kiel, Germany
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  • For correspondence: s.schreiber@mucosa.de
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Abstract

Sarcoidosis is a granulomatous disease that mainly affects the lung. A role of microbial factors in disease pathogenesis is assumed, but has not been investigated systematically in a large cohort.

This cross-sectional study compared the lung microbiota of 71 patients with sarcoidosis, 15 patients with idiopathic pulmonary fibrosis (non-infectious controls) and 10 healthy controls (HCs). Next-generation sequencing of 16S DNA was used on bronchoalveolar lavage samples to characterise the microbial composition, which was analysed for diversity and indicator species. Host genotypes for 13 known sarcoidosis risk variants were determined and correlated with microbial parameters.

The microbial composition differed significantly between sarcoidosis and HC samples (redundancy analysis ANOVA, p=0.025) and between radiographic Scadding types. Atopobium spp. was detected in 68% of sarcoidosis samples, but not in HC samples. Fusobacterium spp. was significantly more abundant in sarcoidosis samples compared with those from HCs. Mycobacteria were found in two of 71 sarcoidosis samples. Host-genotype analysis revealed an association of the rs2076530 (BTNL2) risk allele with a decrease in bacterial burden (p=0.002).

Our results indicate Scadding type-dependent microbiota in sarcoidosis BAL samples. Atopobium spp. and Fusobacterium spp. were identified as sarcoidosis-associated bacteria, which may enable new insights into the pathogenesis and treatment of the disease.

Abstract

Sarcoidosis lung microbial profiles http://ow.ly/IfTC30gxm2U

Footnotes

  • This article has supplementary material available from erj.ersjournals.com

  • Support statement: The study was supported by the Deutsche Forschungsgemeinschaft (DFG) through the Cluster of Excellence ‘Inflammation at Interfaces’. The BioMaterialBank North is funded in part by the Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), and is a member of the PopGen 2.0 network (P2N), which is supported by a grant from the German Ministry for Education and Research (01EY1103). Funding information for this article has been deposited with the Crossref Funder Registry.

  • Conflict of interest: None declared.

  • Received April 13, 2016.
  • Accepted August 28, 2017.
  • Copyright ©ERS 2017
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Atopobium and Fusobacterium as novel candidates for sarcoidosis-associated microbiota
Alexandra Zimmermann, Henrik Knecht, Robert Häsler, Gernot Zissel, Karoline I. Gaede, Sylvia Hofmann, Almut Nebel, Joachim Müller-Quernheim, Stefan Schreiber, Annegret Fischer
European Respiratory Journal Dec 2017, 50 (6) 1600746; DOI: 10.1183/13993003.00746-2016

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Atopobium and Fusobacterium as novel candidates for sarcoidosis-associated microbiota
Alexandra Zimmermann, Henrik Knecht, Robert Häsler, Gernot Zissel, Karoline I. Gaede, Sylvia Hofmann, Almut Nebel, Joachim Müller-Quernheim, Stefan Schreiber, Annegret Fischer
European Respiratory Journal Dec 2017, 50 (6) 1600746; DOI: 10.1183/13993003.00746-2016
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