Purpose 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.
Purpose There is a high disease burden associated with community-acquired pneumonia (CAP) around the world. A timely and correct diagnosis of CAP can facilitate early treatment and prevent illness progression. The present study aimed to find some novel biomarkers of CAP by metabolic analysis and construct a nomogram model for precise diagnosis and individualized treatment of CAP patients. Patients and Methods 42 CAP patients and 20 controls were enrolled in this study. The metabolic profiles of bronchoalveolar lavage fluid (BALF) samples were identified by untargeted LC-MS/MS analysis. With a VIP score ≥ 1 in OPLS-DA analysis and P < 0.05, the significantly dysregulated metabolites were estimated as potential biomarkers of CAP, which were further included in the construction of the diagnostic prediction model along with laboratory inflammatory indexes via stepwise backward regression analysis. Discrimination, calibration, and clinical applicability of the nomogram were evaluated by the C-index, the calibration curve, and the decision curve analysis (DCA) estimated by bootstrap resampling. Results The metabolic profiles differed obviously between CAP patients and healthy controls, as shown by PCA and OPLS-DA plots. Seven metabolites significantly dysregulated in CAP were established: dimethyl disulfide, oleic acid (d5), N-acetyl-a-neuraminic acid, pyrimidine, choline, LPC (12:0/0:0) and PA (20:4/2:0). Multivariate logistic regression revealed that the expression levels of PA (20:4/2:0), N-acetyl-a-neuraminic acid, and CRP were associated with CAP. After being validated by bootstrap resampling, this model showed satisfactory diagnostic performance. Conclusion A novel nomogram prediction model containing metabolic potential biomarkers in BALF that was developed for the early diagnosis of CAP offers insights into the pathogenesis and host response in CAP.
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