The lower airways microbiota and antimicrobial peptides indicate dysbiosis in sarcoidosis

Rationale: The role of the pulmonary microbiome in sarcoidosis is unknown.

Objectives: The objectives of the current study was to: 1) Examine whether the pulmonary fungal and bacterial microbiota differed in patients with sarcoidosis compared with controls. 2) Examine whether there was an association between the microbiota and levels of the antimicrobial peptides (AMPs) in protected bronchoalveolar lavage (PBAL), indicating an interaction with the innate immune response.

Methods: 35 sarcoidosis patients and 35 healthy controls underwent bronchoscopy and were sampled with oral wash (OW), protected BAL (PBAL) and left protected sterile brushes (LPSB).  The fungal ITS1 region and the V3V4 region of the bacterial 16SrDNA gene were sequenced. Bioinformatic analyses were performed with QIIME 2. The AMPs secretory leucocyte protease inhibitor (SLPI) and human beta defensins 1 and 2 (hBD-1 & hBD-2), were measured in PBAL by enzyme linked immunosorbent assay (ELISA).

Measurements and Main Results: Aspergillus dominated the PBAL samples in sarcoidosis. Differences in bacterial taxonomy were minor. There was no significant difference in fungal alpha diversity between sarcoidosis and controls, but the bacterial  alpha diversity in sarcoidosis was significantly lower in OW (p=0.047) and PBAL (p=0.03) compared with controls. The beta diversity for sarcoidosis compared with controls differed for both fungi and bacteria. AMP levels were significantly lower in sarcoidosis compared to controls (SLPI & hBD-1: p<0.01). No significant correlations were found between a-diversity and AMPs.

Conclusions: The pulmonary fungal and bacterial microbiota in sarcoidosis differed from controls, with lower antimicrobial peptides levels in sarcoidosis.

Methods
The dataset is part of the larger Bergen COPD Microbiome Study ("MicroCOPD") and Bergen ILD Microbiome Study ("MicroILD").  Processing details can be viewed in the paper & its supplement.