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

Abstract

Yukun He,1 Wenyi Yu,1 Pu Ning,1,2 Qiongzhen Luo,1,3 Lili Zhao,1 Yu Xie,1 Yan Yu,1 Xinqian Ma,1 Li Chen,1 Yali Zheng,1,4 Zhancheng Gao1,4 1Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Respiratory & Critical Care Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 4Department of Respiratory, Critical Care, and Sleep Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of ChinaCorrespondence: Yali ZhengDepartment of Respiratory, Critical Care, and Sleep Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of ChinaEmail [email protected] GaoDepartment of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaEmail [email protected]: 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.Keywords: community-acquired pneumonia, connective tissue disease-associated interstitial disease, microbiome, metabolome, shared and specific alterations

Keywords

• community-acquired pneumonia
• connective tissue disease-associated interstitial disease
• microbiome
• metabolome
• shared and specific alterations