Characterization of the Microbiome and Host’s Metabolites of the Lower Respiratory Tract During Acute Community-Acquired Pneumonia Identifies Potential Novel Markers

Qiang Xiao,1,&ast; Shukun Tan,1,2,&ast; Changzhi Liu,3,&ast; Bin Liu,1 Yingxiong Li,1 Yehui Guo,1 Peiyan Hu,1 Zhuoying Su,1 Siqin Chen,1 Wei Lei,1 Xi Li,1 Minhong Su,4 Fu Rong1 1Pulmonary and Critical Care Medicine, Shunde Hospital, Southern Medical University (the First People’s Hospital of Shunde Foshan), Foshan, 528300, People’s Republic of China; 2Respiratory Medicine of the Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, 528222, People’s Republic of China; 3Critical Care Medicine, Shunde Hospital, Southern Medical University (the First People’s Hospital of Shunde Foshan), Foshan, 528300, People’s Republic of China; 4Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fu Rong, Pulmonary and Critical Care Medicine, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), No. 1, Jiazi Road, Lunjiao Street, Shunde District, Foshan, 528300, People’s Republic of China, Tel +86-757-22318689, Email rongfu828@sina.com Minhong Su, Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, 253 Gongye Middle Avenue, Haizhu District, Guangzhou, 510280, People’s Republic of China, Tel +86-20-62782290, Email 878697159@qq.comPurpose: Community-acquired pneumonia (CAP) is one of the most frequently encountered infectious diseases worldwide. Few studies have explored the microbial composition of the lower respiratory tract (LRT) and host metabolites of CAP. We analyzed the microbial composition of the LRT and levels of host metabolites to explore new biomarkers for CAP.Patients and Methods: Bronchoalveolar lavage fluid (BALF) was collected from 28 CAP patients and 20 healthy individuals. Following centrifugation, BALF pellets were used for amplicon sequencing of a variable region of the bacterial 16S rDNA gene to characterize the microbial composition. Non-targeted metabolomics was used to detect host’s metabolites in the supernatant.Results: Compared with healthy individuals, the bacterial alpha diversity in the LRT of CAP patients was significantly lower in CAP patients (p< 0.05). On the bacterial genus level, over 20 genera were detected with lower relative abundance (p< 0.05), while the relative abundance of Ruminiclostridium-6 was significantly higher in CAP patients. The levels of the host metabolites dimethyldisulfide, choline, pyrimidine, oleic acid and N-acetyl-neuraminic acid were all increased in BALF of CAP patients (p< 0.05), while concentrations of lysophosphatidylcholines (LPC (12:0/0:0)) and phosphatidic acid (PA (20:4/2:0)) were decreased (p< 0.05). Furthermore, the relative abundance of Parvimonas, Treponema-2, Moraxella, Aggregatibacter, Filifactor, Fusobacterium, Lautropia and Neisseria negatively correlated with concentrations of oleic acid (p< 0.05). A negative correlation between the relative abundance of Treponema-2, Moraxella, Filifactor, Fusobacterium and dimethyldisulfide concentrations was also observed (p< 0.05). In contrast, the relative abundance of Treponema-2, Moraxella, Filifactor, and Fusobacterium was found to be positively associated with concentrations of LPC (12:0/0:0) and PA (20:4/2:0) (p< 0.05).Conclusion: The composition of the LRT microbiome differed between healthy individuals and CAP patients. We propose that some respiratory microbial components and host metabolites are potentially novel diagnostic markers of CAP.Keywords: community-acquired pneumonia, microbiome, metabolites, biomarker, diagnosis