Comparison of lung microbiota between antineutrophil cytoplasmic antibody-associated vasculitis and sarcoidosis

Abstract

Microbial involvement in the pathogenesis have been suggested in both antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and sarcoidosis, both of which have lung involvement. However, exhaustive research to assess the bacteria in the lung in AAV and in sarcoidosis have not been performed. We sought to elucidate the distinct dysbiotic lung microbiota between AAV and sarcoidosis. We used 16S rRNA gene high-throughput sequencing to obtain the bacterial community composition of bronchoalveolar lavage fluid (BALF) in patients with AAV (n = 16) compared to patients with sarcoidosis (n = 21). The patients had not undergone therapy with immunosuppressive medication when their BALF was acquired. No difference was observed in α-diversity between patients with AAV and patients with sarcoidosis when using all the detected taxa. We defined the taxa of the oral cavity by using the data of oral microbiota of healthy individuals from the Human Microbiome Project (HMP). The analysis using only oral taxa made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. Besides, the analysis using detected taxa except for oral taxa also made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. A linear negative relationship between the α-diversity and Birmingham vasculitis activity score (BVAS) was detected in the AAV group. The observed p-value for the effect of the disease groups on the ß-diversity was small while the effect of other factors including sex and smoking status did not have small p-values. By excluding oral taxa from all the detected taxa, we found a cluster mainly consisted of sarcoidosis patients which was characterized with microbial community monopolized by Erythrobacteraceae family. Our results suggested the importance of considering the influence of oral microbiota in evaluating lung microbiota. Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are forms of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a systemic disease affecting multiple organs including the lungs and kidneys. The production of ANCA, playing a pathogenetic role in AAV, is thought to be initiated by exogenous or endogenous antigens including microbes, drugs, or dysregulated autoantigen expression 1. Patients

Lung microbiome: new insights into the pathogenesis of respiratory diseases

“…The most abundant genera in sarcoidosis BALF were Streptococcus , Prevotella, and Veillonella , 370 , 371 which is consistent with previous studies on the compositions of the healthy lung microbiome. 31 , 57 The specificity lies in the fact that a taxon composed mainly of patients with sarcoidosis featured a microbiota monopolized by the Erythrobacteraceae family, 370 as well as Mycobacterium 372 and Propionibacterium acnes . 373 In addition, Atopobium and Clostridium were abundantly present in the microbiota and associated with sarcoidosis.…”

“…Several infectious agents have been suggested as possible pathogens of sarcoidosis, including Mycobacterium and Propionibacterium acnes (P. acnes). 369 The most abundant genera in sarcoidosis BALF were Streptococcus, Prevotella, and Veillonella, 370,371 which is consistent with previous studies on the compositions of the healthy lung microbiome. 31,57 The specificity lies in the fact that a taxon composed mainly of patients with sarcoidosis featured a microbiota monopolized by the Erythrobacteraceae family, 370 as well as Mycobacterium 372 and Propionibacterium acnes.…”

The lower airways microbiota and antimicrobial peptides indicate dysbiosis in sarcoidosis

“…In another study of the bacterial microbiota with 71 sarcoidosis patients, 15 IPF patients, and 10 healthy controls, BAL measurements revealed more Fusobacterium spp and Atopobium spp in sarcoidosis compared to healthy controls [ 8 ]. Fukui et al compared lung microbiota between patients with sarcoidosis and anti-neutrophil cytoplasmic antibody-associated (ANCA) vasculitis, and found clustering of the Erythrobacteraceae family in sarcoidosis patients [ 11 ]. Gupta et al performed a comparative analysis of the alveolar microbiome in 27 COPD patients, 8 ILD and 8 sarcoidosis patients and found Actinobacteria and Proteobacteria to be significantly more abundant in sarcoidosis patients compared to ILD patients [ 12 ].…”

“…A small number of studies have investigated the pulmonary bacterial microbiota in sarcoidosis, exploring whether the sarcoid lower airways microbiome was different from healthy controls [ 5 , 7 , 8 ] or other patient groups [ 9 – 12 ]. The results have been inconsistent, with three studies finding differences [ 8 , 11 , 12 ] and four not [ 5 , 7 , 9 , 10 ].…”

“…In sarcoidosis, only two studies to our knowledge have been published on the pulmonary fungal microbiota and they both detected enrichment of Aspergillus [5,6]. A small number of studies have investigated the pulmonary bacterial microbiota in sarcoidosis, exploring whether the sarcoid lower airways microbiome was different from healthy controls [5,7,8] or other patient groups [9][10][11][12]. The results have been inconsistent, with three studies finding differences [8,11,12] and four not [5,7,9,10].…”