TY - JOUR
T1 - Bacterial and Viral Respiratory Tract Microbiota and Host Characteristics in Adults With Lower Respiratory Tract Infections
T2 - A Case-Control Study
AU - Haak, Bastiaan W.
AU - Brands, Xanthe
AU - Davids, Mark
AU - Peters-Sengers, Hessel
AU - Kullberg, Robert F. J.
AU - van Houdt, Robin
AU - Hugenholtz, Floor
AU - Faber, Daniël R.
AU - Zaaijer, Hans L.
AU - Scicluna, Brendon P.
AU - van der Poll, Tom
AU - Wiersinga, W. Joost
N1 - Funding Information: This work was supported by the Netherlands Organization for Scientific Research (VIDI grant number 91716475 to W. J. W.), and the Netherlands Organization for Health Research and Development (ZonMW grant number 50-53000-98-139 to X. B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021 The Author(s).
PY - 2022/3/1
Y1 - 2022/3/1
N2 - Background: Viruses and bacteria from the nasopharynx are capable of causing community-acquired pneumonia (CAP), which can be difficult to diagnose. We aimed to investigate whether shifts in the composition of these nasopharyngeal microbial communities can be used as diagnostic biomarkers for CAP in adults. Methods: We collected nasopharyngeal swabs from adult CAP patients and controls without infection in a prospective multicenter case-control study design. We generated bacterial and viral profiles using 16S ribosomal RNA gene sequencing and multiplex polymerase chain reaction (PCR), respectively. Bacterial, viral, and clinical data were subsequently used as inputs for extremely randomized trees classification models aiming to distinguish subjects with CAP from healthy controls. Results: We enrolled 117 cases and 48 control subjects. Cases displayed significant beta diversity differences in nasopharyngeal microbiota (P = .016, R2 =. 01) compared to healthy controls. Our extremely randomized trees classification models accurately discriminated CAP caused by bacteria (area under the curve [AUC]. 83), viruses (AUC. 95) or mixed origin (AUC. 81) from healthy control subjects. We validated this approach using a dataset of nasopharyngeal samples from 140 influenza patients and 38 controls, which yielded highly accurate (AUC. 93) separation between cases and controls. Conclusions: Relative proportions of different bacteria and viruses in the nasopharynx can be leveraged to diagnose CAP and identify etiologic agent(s) in adult patients. Such data can inform the development of a microbiota-based diagnostic panel used to identify CAP patients and causative agents from nasopharyngeal samples, potentially improving diagnostic specificity, efficiency, and antimicrobial stewardship practices.
AB - Background: Viruses and bacteria from the nasopharynx are capable of causing community-acquired pneumonia (CAP), which can be difficult to diagnose. We aimed to investigate whether shifts in the composition of these nasopharyngeal microbial communities can be used as diagnostic biomarkers for CAP in adults. Methods: We collected nasopharyngeal swabs from adult CAP patients and controls without infection in a prospective multicenter case-control study design. We generated bacterial and viral profiles using 16S ribosomal RNA gene sequencing and multiplex polymerase chain reaction (PCR), respectively. Bacterial, viral, and clinical data were subsequently used as inputs for extremely randomized trees classification models aiming to distinguish subjects with CAP from healthy controls. Results: We enrolled 117 cases and 48 control subjects. Cases displayed significant beta diversity differences in nasopharyngeal microbiota (P = .016, R2 =. 01) compared to healthy controls. Our extremely randomized trees classification models accurately discriminated CAP caused by bacteria (area under the curve [AUC]. 83), viruses (AUC. 95) or mixed origin (AUC. 81) from healthy control subjects. We validated this approach using a dataset of nasopharyngeal samples from 140 influenza patients and 38 controls, which yielded highly accurate (AUC. 93) separation between cases and controls. Conclusions: Relative proportions of different bacteria and viruses in the nasopharynx can be leveraged to diagnose CAP and identify etiologic agent(s) in adult patients. Such data can inform the development of a microbiota-based diagnostic panel used to identify CAP patients and causative agents from nasopharyngeal samples, potentially improving diagnostic specificity, efficiency, and antimicrobial stewardship practices.
KW - 16S rRNA sequencing
KW - community-acquired pneumonia
KW - influenza
KW - microbiome
KW - nasopharynx
UR - http://www.scopus.com/inward/record.url?scp=85126152596&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/cid/ciab568
DO - https://doi.org/10.1093/cid/ciab568
M3 - Article
C2 - 34156449
SN - 1058-4838
VL - 74
SP - 776
EP - 784
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 5
ER -