Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis

Takahashi, Youhei; Saito, Atsushi; Chiba, Hirofumi; Kuronuma, Koji; Ikeda, Kimiyuki; Kobayashi, Takeaki; Ariki, Shigeru; Takahashi, Motoko; Sasaki, Yasushi; Takahashi, Hiroki

doi:10.1186/s12931-018-0736-9

Cited by 62 publications

(51 citation statements)

References 30 publications

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“…Based on the reported bacterial topography data we can assume that the lung luminal and tissue-resident microbes described here have migrated primarily by microaspiration and additionally by mucosal dispersion from the upper respiratory track ( Dickson et al, 2017 ). The similar frequency of the BALF microbial communities at phylum level in healthy individuals and IPF patients between our findings and previous reports suggests that contamination was probably minimum in our present study ( Molyneaux et al, 2017 ; Takahashi et al, 2018 ). The risk of contamination of lung tissues sampled from IPF and lung cancer patients, and of the lungs excised from WT and TGF-β1 TG mice was also minimum, at least during sampling, because sampling was performed under sterile surgical conditions.…”

Section: Discussionsupporting

confidence: 91%

Identification of Halophilic Microbes in Lung Fibrotic Tissue by Oligotyping

et al. 2018

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Idiopathic pulmonary fibrosis (IPF) is an incurable disease with poor prognosis and unknown etiology. The poor clinical outcome is associated with enhanced microbial burden in bronchoalveolar lavage fluid from IPF patients. However, whether microbes from the respiratory tract fluid cause the disease remains uncertain. Tissue-associated microbes can influence host physiology in health and disease development. The aim of this study was to evaluate the existence of microbes in lung fibrotic tissues. We evaluated the microbial community in lung tissues from IPF and from human transforming growth factor-β1 (TGF-β1) transgenic mice with lung fibrosis by oligotyping. We also evaluated the microbial population in non-tumor-bearing tissues from surgical specimens of lung cancer patients. The phyla Firmicutes and the genus Clostridium tended to be predominant in the lung tissue from IPF and lung cancer patients. Oligotyping analysis revealed a predominance of bacteria belonging to the genera Halomonas, Shewanella, Christensenella, and Clostridium in lung tissue from IPF and lung cancer. Evaluation of the microbial community in the lung tissue from mice revealed abundance of Proteobacteria in both wild-type (WT) littermates and transgenic mice. However, the genus Halomonas tended to be more abundant in TGF-β1 transgenic mice compared to WT mice. In conclusion, this study describes tissue-associated microbes in lung fibrotic tissues from IPF patients and from aging TGF-β1 transgenic mice.

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Section: Discussionsupporting

confidence: 91%

Identification of Halophilic Microbes in Lung Fibrotic Tissue by Oligotyping

et al. 2018

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“…A previous report showed that bacteria of the Staphylococcus and Streptococcus genera worsen the clinical outcome of IPF patients, suggesting their implication in the disease progression and pathogenesis 7 . Studies showing the relative abundance of Staphylococcus or Streptococcus genera in the fibrotic lung and its significant correlation with the host immune response in IPF patients further support the contribution of these bacteria genera in the pathogenesis of pulmonary fibrosis 6,42,[48][49][50][51][52] . However, the precise mechanism remains unclear.…”

Section: Discussionmentioning

confidence: 87%

A Staphylococcus pro-apoptotic peptide induces acute exacerbation of pulmonary fibrosis

et al. 2020

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Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown etiology; however, apoptosis of lung alveolar epithelial cells plays a role in disease progression. This intractable disease is associated with increased abundance of Staphylococcus and Streptococcus in the lungs, yet their roles in disease pathogenesis remain elusive. Here, we report that Staphylococcus nepalensis releases corisin, a peptide conserved in diverse staphylococci, to induce apoptosis of lung epithelial cells. The disease in mice exhibits acute exacerbation after intrapulmonary instillation of corisin or after lung infection with corisin-harboring S. nepalensis compared to untreated mice or mice infected with bacteria lacking corisin. Correspondingly, the lung corisin levels are significantly increased in human IPF patients with acute exacerbation compared to patients without disease exacerbation. Our results suggest that bacteria shedding corisin are involved in acute exacerbation of IPF, yielding insights to the molecular basis for the elevation of staphylococci in pulmonary fibrosis.

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“…Our clinical observations suggest that rapid worsening or AE of IPF are often preceded by "cold-like" symptoms without clearly establishing an acute infectious respiratory disease. Recently, several studies suggested that progression of IPF seems to be associated with bacterial or viral infection and/or abnormal composition of the lung microbiome, which is a good reason to revisit the definition of AE-IPF [3,[12][13][14][15][16][17]. Afarwal and Jindal [4] have shown that infections are able to induce an inflammatory cascade in the lung of IPF patients, thus leading to a rapid deterioration of stable IPF.…”

Section: Discussionmentioning

confidence: 99%

“…Typical common cold symptoms include cough, worsening dyspnea and mild fever-all of them have been included in the description of AE-IPF events [11]. Further, recent evidence points towards a potential role of an altered lung microbiome in triggering IPF progression, including AE-IPF [12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

The role of infection in acute exacerbation of Idiopathic Pulmonary Fibrosis

Wu¹,

Li²

2018

Idiopathic Interstitial Pneumonias

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Background. Acute exacerbation of IPF (AE-IPF) is associated with high mortality. We studied changes in pathogen involvement during AE-IPF and explored a possible role of infection in AE-IPF. Objectives. Our purpose is to investigate the role of infection in AE-IPF. Methods. Overall, we recruited 170 IPF patients (48 AE-IPF, 122 stable) and 70 controls at Shanghai Pulmonary Hospital. Specific IgM against microbial pathogens and pathogens in sputum were assessed. RNA sequences of pathogens in nasopharyngeal swab of IPF patients were detected by PathChip. A panel of serum parameters reflecting immune function were assessed. Results. Antiviral/bacterial IgM was higher in IPF vs. controls and in AE-IPF vs. stable IPF. Thirty-eight different bacterial strains were detected in IPF patient sputum. Bacteria-positive results were found in 9/48 (18.8%) of AE-IPF and in 26/122 (21.3%) stable IPF. Fifty-seven different viruses were detected in nasopharyngeal swabs of IPF patients. Virus-positive nasopharyngeal swabs were found in 18/30 (60%) of tested AE-IPF and in 13/30 (43.3%) of stable IPF. AE-IPF showed increased inflammatory cytokines (IL-6, IFN-γ, MIG, IL-17, and IL-9) vs. stable IPF and controls. Mortality of AE-IPF in one year (39.5%) was higher compared to stable IPF (28.7%).Conclusions. IPF patients had different colonization with pathogens in sputum and nasopharyngeal swabs; they also displayed abnormally activated immune response, which was exacerbated during AE-IPF.

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Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis

Cited by 62 publications

References 30 publications

Identification of Halophilic Microbes in Lung Fibrotic Tissue by Oligotyping

Identification of Halophilic Microbes in Lung Fibrotic Tissue by Oligotyping

A Staphylococcus pro-apoptotic peptide induces acute exacerbation of pulmonary fibrosis

The role of infection in acute exacerbation of Idiopathic Pulmonary Fibrosis

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