The upper and lower respiratory tract microbiome in severe aspiration pneumonia

Georgios D Kitsios; Vi D Nguyen; Khaled Sayed; Nameer Al-Yousif; Caitlin Schaefer; Faraaz A Shah; William Bain; Haopu Yang; Adam Fitch; Kelvin Li; Xiaohong Wang; Shulin Qin; Heather Gentry; Yingze Zhang; Jack Varon; Antonio Arciniegas Rubio; Joshua A Englert; Rebecca M Baron; Janet S Lee; Barbara Methé; Panayiotis V Benos; Alison Morris; Bryan J McVerry

doi:10.1016/j.isci.2023.106832

The upper and lower respiratory tract microbiome in severe aspiration pneumonia

iScience. 2023 May 6;26(6):106832. doi: 10.1016/j.isci.2023.106832. eCollection 2023 Jun 16.

Authors

Georgios D Kitsios^{1

2

3

4}, Vi D Nguyen^{2

5}, Khaled Sayed^{6

7}, Nameer Al-Yousif⁸, Caitlin Schaefer^{1

4}, Faraaz A Shah^{1

2

4

9}, William Bain^{1

2

4

9}, Haopu Yang^{2

10}, Adam Fitch³, Kelvin Li³, Xiaohong Wang¹, Shulin Qin^{1

3}, Heather Gentry¹, Yingze Zhang^{1

4}, Jack Varon¹¹, Antonio Arciniegas Rubio¹¹, Joshua A Englert¹², Rebecca M Baron¹¹, Janet S Lee¹³, Barbara Methé^{1

3}, Panayiotis V Benos⁷, Alison Morris^{1

2

3

14}, Bryan J McVerry^{1

2

3

4}

Affiliations

¹ Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA15213, USA.
² University of Pittsburgh School of Medicine, Pittsburgh, PA15213, USA.
³ Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, PA15213, USA.
⁴ Acute Lung Injury Center for Excellence, Department of Medicine, University of Pittsburgh, Pittsburgh, PA15213, USA.
⁵ University of California Los Angeles, Department of Medicine, Internal Medicine Residency Program, Los Angeles, CA90095, USA.
⁶ University of PittsburghDepartment of Computational & Systems Biology, Pittsburgh, PA15213, USA.
⁷ Department of Epidemiology, University of Florida, Gainesville, FL32611, USA.
⁸ University of Pittsburgh Medical Center Mercy, Department of Medicine, Pittsburgh, PA15219, USA.
⁹ Veteran's Affairs Pittsburgh Healthcare System, Pittsburgh, PA15240, USA.
¹⁰ School of Medicine, Tsinghua University, Beijing, China.
¹¹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA02115, USA.
¹² Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH43210, USA.
¹³ Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO63110, USA.
¹⁴ Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA15213, USA.

Abstract

Uncertainty persists whether anaerobic bacteria represent important pathogens in aspiration pneumonia. In a nested case-control study of mechanically ventilated patients classified as macro-aspiration pneumonia (MAsP, n = 56), non-macro-aspiration pneumonia (NonMAsP, n = 91), and uninfected controls (n = 11), we profiled upper (URT) and lower respiratory tract (LRT) microbiota with bacterial 16S rRNA gene sequencing, measured plasma host-response biomarkers, analyzed bacterial communities by diversity and oxygen requirements, and performed unsupervised clustering with Dirichlet Multinomial Models (DMM). MAsP and NonMAsP patients had indistinguishable microbiota profiles by alpha diversity and oxygen requirements with similar host-response profiles and 60-day survival. Unsupervised DMM clusters revealed distinct bacterial clusters in the URT and LRT, with low-diversity clusters enriched for facultative anaerobes and typical pathogens, associated with higher plasma levels of SPD and sCD14 and worse 60-day survival. The predictive inter-patient variability in these bacterial profiles highlights the importance of microbiome study in patient sub-phenotyping and precision medicine approaches for severe pneumonia.

Keywords: Clinical finding; Microbiome; Respiratory medicine.

Grants and funding

IK2 BX004886/BX/BLRD VA/United States