Lung Microbiota in Idiopathic Pulmonary Fibrosis, Hypersensitivity Pneumonitis, and Unclassified Interstitial Lung Diseases: A Preliminary Pilot Study

Abstract

(1) Introduction: Although historically, the lung has been considered a sterile organ, recent studies through 16S rRNA gene sequencing have identified a substantial number of microorganisms. The human microbiome has been considered an "essential organ," carrying about 150 times more information (genes) than are found in the entire human genome. The purpose of the present study is to characterize and compare the microbiome in three different interstitial lung diseases: idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, and nondifferential interstitial lung disease. (2) Material and methods: This was a prospective cohort study where the DNA of 28 patients with ILD was extracted from the lavage and then processed using the standard technique of 16S RNA gene sequencing. In a tertiary teaching hospital in the northern, western part of Romania, samples were collected through bronchoscopy and then processed. (3) Results: The same four species were found in all the patients but in different quantities and compositions: Firmicutes, Actinobacteria, Proteobacteria and Bacteroides. Streptococcus was the most prevalent genus, followed by Staphylococcus and Prevotella. Statistically significant differences in the OUT count for the ten most abundant taxa were found for the genus: Gemella, Actinobacteria, Prevotella, Neisseria, Haemophilus, and Bifidobacterium. The comparative analysis showed a richer microbiota in patients with IPF, as shown by the alpha diversity index. (4) Conclusions: In interstitial lung diseases, the microorganisms normally found in the lung are reduced to a restricted flora dominated by the Firmicutes family. These changes significantly disrupt the continuity of the observed bacterial pattern from the oropharynx to the bronchial tree and lung, possibly impacting the evolution and severity of interstitial lung diseases.

Keywords: hypersensitivity pneumonitis; idiopathic pulmonary fibrosis; interstitial lung disease; lung microbiome; lung microbiota.

Figure 1

Krona diagram of the microbial profile of (A) a sample of HP, (B) IPF, and (C) a sample of unclassifiable ILD.

Figure 1

Krona diagram of the microbial profile of (A) a sample of HP, (B) IPF, and (C) a sample of unclassifiable ILD.

Figure 1

Krona diagram of the microbial profile of (A) a sample of HP, (B) IPF, and (C) a sample of unclassifiable ILD.

Figure 2

The average percentage of bacterial families found in the three groups.

Figure 3

Alpha diversity plots for the study’s three patient groups: (A) Observed OTUs, (B) Chao 1; (C) Shannon index, and (D) inverse Simpson index. “*” represent the p value of the analysis, which in our case is <0.05, which means the different is statistical significant. Blue—patients with idiopathic pulmonary fibrosis; Red—patients with hypersensitivity pneumonitis; Green—patients with unclassified ILDs (interstitial lung diseases).

Figure 4

Euclidean PCoA plots: (A) all samples, (B) HP samples, (C) IPF samples, and (D) unclassifiable ILD. IPF—idiopathic pulmonary fibrosis; HP—hypersensitivity pneumonitis; Unclassified ILDs—unclassified interstitial lung disease.

Figure 5

Most abundant taxa at the genus level for the three groups. IPF—idiopathic pulmonary fibrosis; HP—hypersensitivity pneumonitis; Unclassified ILDs—unclassified interstitial lung disease.

Figure 6

Comparison of OTU counts for IPF compared to HP and undifferentiated ILD (A) Gemella, (B) Actinobacteria, (C) Prevotella, (D) Neisseria, (E) Haemophilus, and (F) Bifidobacterium. “*”is the p value of the analysis and is < 0.05; “**”is the p value of the analysis and is < 0.005. Blue—patients with IPF—idiopathic pulmonary fibrosis; Red—patients with HP—hypersensitivity pneumonitis; Green—patients with Unclassified ILDs—unclassified interstitial lung disease.