Correlation of the lung microbiota with metabolic profiles in bronchoalveolar lavage fluid in HIV infection

• Type of Material: Article
• Authors: Sushma Cribbs, Emory University; Karan Uppal, Emory University; Shuzhao Li, Emory University; Dean Jones, Emory University; Alison Morris, University of Pittsburgh; Laurence Huang, University of California, San Francisco; Laura Tipton, University of Pittsburgh; Adam Fitch, University of Pittsburgh; Ruth M. Greenblatt, University of California, San Francisco; Lawrence Kingsley, University of Pittsburgh; David Guidot, Emory University; Elodie Ghedin, New York University
• Language: English
• Date: 2016-01-20
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © Cribbs et al. 2016. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s40168-016-0147-4
• Title of Journal or Parent Work: Microbiome
• ISSN: 2049-2618
• Volume: 4
• Issue: 1
• Start Page: 3
• End Page: 3
• Grant/Funding Information: NIH HL113451 (D.J.); NIH R01 HL090339, K24 HL123342 (A.M.); U01 HL098962 (A.M., E.G.); K24HL123342; HL087713 (LH); NIAID and NCI UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UL1TR000124 (UCLA CTRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041 (Multicenter AIDS Cohort); NIAID and NICHHD UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590, and UO1-HD-32632 (WIHS).
• Keywords: Microbiota; Life Sciences & Biomedicine; CELLS; Microbiology; Lung; HIV; Metabolomics; Bronchoalveolar lavage; PNEUMONIA; CYSTEINE; OXIDATIVE STRESS; Science & Technology; DIFFUSING-CAPACITY; CD4(+)
• Research Categories: Biology, Microbiology; Health Sciences, Pathology

Abstract

BACKGROUND: While 16S ribosomal RNA (rRNA) sequencing has been used to characterize the lung's bacterial microbiota in human immunodeficiency virus (HIV)-infected individuals, taxonomic studies provide limited information on bacterial function and impact on the host. Metabolic profiles can provide functional information on host-microbe interactions in the lungs. We investigated the relationship between the respiratory microbiota and metabolic profiles in the bronchoalveolar lavage fluid of HIV-infected and HIV-uninfected outpatients. RESULTS: Targeted sequencing of the 16S rRNA gene was used to analyze the bacterial community structure and liquid chromatography-high-resolution mass spectrometry was used to detect features in bronchoalveolar lavage fluid. Global integration of all metabolic features with microbial species was done using sparse partial least squares regression. Thirty-nine HIV-infected subjects and 20 HIV-uninfected controls without acute respiratory symptoms were enrolled. Twelve mass-to-charge ratio (m/z) features from C18 analysis were significantly different between HIV-infected individuals and controls (false discovery rate (FDR) = 0.2); another 79 features were identified by network analysis. Further metabolite analysis demonstrated that four features were significantly overrepresented in the bronchoalveolar lavage (BAL) fluid of HIV-infected individuals compared to HIV-uninfected, including cystine, two complex carbohydrates, and 3,5-dibromo-L-tyrosine. There were 231 m/z features significantly associated with peripheral blood CD4 cell counts identified using sparse partial least squares regression (sPLS) at a variable importance on projection (VIP) threshold of 2. Twenty-five percent of these 91 m/z features were associated with various microbial species. Bacteria from families Caulobacteraceae, Staphylococcaceae, Nocardioidaceae, and genus Streptococcus were associated with the greatest number of features. Glycerophospholipid and lineolate pathways correlated with these bacteria. CONCLUSIONS: In bronchoalveolar lavage fluid, specific metabolic profiles correlated with bacterial organisms known to play a role in the pathogenesis of pneumonia in HIV-infected individuals. These findings suggest that microbial communities and their interactions with the host may have functional metabolic impact in the lung.