Shared and Specific Lung Microbiota with Metabolic Profiles in Bronchoalveolar Lavage Fluid Between Infectious and Inflammatory Respiratory Diseases

Abstract

Background: Infiltration of the lower respiratory tract (LRT) microenvironment could be significantly associated with respiratory diseases. However, alterations in the LRT microbiome and metabolome in infectious and inflammatory respiratory diseases and their correlation with inflammation still need to be explored. Methods: Bronchoalveolar lavage samples from 44 community-acquired pneumonia (CAP) patients, 29 connective tissue disease-associated interstitial disease (CTD-ILD) patients, and 30 healthy volunteers were used to detect microbiota and metabolites through 16S rRNA gene sequencing and untargeted high-performance liquid chromatography with mass spectrometry. Results: The composition of the LRT microbial communities and metabolites differed in disease states. CAP patients showed a significantly low abundance and both diseases presented a depletion of some genera of the phylum Bacteroidetes, including Prevotella, Porphyromonas, and health-associated metabolites, such as sphingosine (d16:1), which were negatively correlated with infectious indicators. In contrast, Bacillus and Mycoplasma were both enriched in the disease groups. Streptococcus was specifically increased in CTD-ILD. In addition, co-elevated metabolites such as FA (22:4) and pyruvic acid represented hypoxia and inflammation in the diseases. Significantly increased levels of amino acids and succinate, as well as decreased itaconic acid levels, were observed in CAP patients, whereas CTD-ILD patients showed only a handful of specific metabolic alterations. Functions related to microbial lipid and amino acid metabolism were significantly altered, indicating the possible contributions of microbial metabolism. Dual omics analysis showed a moderate positive correlation between the microbiome and metabolome. The levels of L-isoleucine and L-arginine were negatively correlated with Streptococcus, and itaconic acid positively correlated with Streptococcus. Conclusion: In the LRT microenvironment, shared and specific alterations occurred in CAP and CTD-ILD patients, which were associated with inflammatory and immune reactions, which may provide a new direction for future studies aiming to elucidate the mechanism, improve the diagnosis, and develop therapies for different respiratory diseases.

Defining the baseline of pulmonary microbiota in healthy populations and influencing factors

“…In Fig. 1, we found the main bacterial phyla in the United States [32][33][34], Asia [35][36][37][38][39] and Europe [40][41][42][43] remain completely consistent. In the normal tissues of patients [44][45][46][47][48][49], four main bacterial phyla (Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes) were shared with healthy subjects.…”

Microbiome features in bronchoalveolar lavage fluid of patients with idiopathic inflammatory myopathy-related interstitial lung disease

“…Prevotella is known to promote the production of inflammatory cytokines, but the genus contains many different species, some of which may play different roles than other members. Yukun He reported that the abundance of Prevotella was decreased in both CAP and CTD-ILD patients and was negatively correlated with white blood cell counts and CRP levels ( 1 ). Unfortunately, we did not get that result.…”

“…Connective tissue disease-associated interstitial lung disease (CTD-ILD) and community-acquired pneumonia (CAP) are heterogeneous lung diseases ( 1 ). They are all characterized by inflammatory lesions in the lungs.…”

Characteristics of lower respiratory tract microbiota in the patients with post-hematopoietic stem cell transplantation pneumonia

“…For patients diagnosed with pneumonia, bronchoscopy was performed as a part of clinical management within 72 h after hospital admission before the ventilation treatments. Detailed sampling procedures, pretreatment, and storage were performed as described in previous studies ( Zheng et al., 2019 ; He et al., 2022 ). Sampling controls were collected through simulated bronchoscopy procedures (no patient) using the same instrument and method.…”