Distinct lung microbiota associate with HIV-associated chronic lung disease in children

Abstract Chronic lung disease (CLD) is a common co-morbidity for HIV-positive children and adolescents on antiretroviral therapy (ART) in sub-Saharan Africa. In this population, distinct airway microbiota may differentially confer risk of CLD. In a cross-sectional study of 202 HIV-infected children...

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Main Authors: Sudha Bhadriraju, Douglas W. Fadrosh, Meera K. Shenoy, Din L. Lin, Kole V. Lynch, Kathryn McCauley, Rashida A. Ferrand, Edith D. Majonga, Grace McHugh, Laurence Huang, Susan V. Lynch, John Z. Metcalfe
Format: Article
Language:English
Published: Nature Portfolio 2020-09-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-73085-1
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author Sudha Bhadriraju
Douglas W. Fadrosh
Meera K. Shenoy
Din L. Lin
Kole V. Lynch
Kathryn McCauley
Rashida A. Ferrand
Edith D. Majonga
Grace McHugh
Laurence Huang
Susan V. Lynch
John Z. Metcalfe
author_facet Sudha Bhadriraju
Douglas W. Fadrosh
Meera K. Shenoy
Din L. Lin
Kole V. Lynch
Kathryn McCauley
Rashida A. Ferrand
Edith D. Majonga
Grace McHugh
Laurence Huang
Susan V. Lynch
John Z. Metcalfe
author_sort Sudha Bhadriraju
collection DOAJ
description Abstract Chronic lung disease (CLD) is a common co-morbidity for HIV-positive children and adolescents on antiretroviral therapy (ART) in sub-Saharan Africa. In this population, distinct airway microbiota may differentially confer risk of CLD. In a cross-sectional study of 202 HIV-infected children aged 6–16 years in Harare, Zimbabwe, we determined the association of sputum microbiota composition (using 16S ribosomal RNA V4 gene region sequencing) with CLD defined using clinical, spirometric, or radiographic criteria. Forty-two percent of children were determined to have CLD according to our definition. Dirichlet multinomial mixtures identified four compositionally distinct sputum microbiota structures. Patients whose sputum microbiota was dominated by Haemophilus, Moraxella or Neisseria (HMN) were at 1.5 times higher risk of CLD than those with Streptococcus or Prevotella (SP)-dominated microbiota (RR = 1.48, p = 0.035). Cell-free products of HMN sputum microbiota induced features of epithelial disruption and inflammatory gene expression in vitro, indicating enhanced pathogenic potential of these CLD-associated microbiota. Thus, HIV-positive children harbor distinct sputum microbiota, with those dominated by Haemophilus, Moraxella or Neisseria associated with enhanced pathogenesis in vitro and clinical CLD.
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spelling doaj.art-5c889e806c114c2e94ed9a46227d7dc52022-12-21T22:43:45ZengNature PortfolioScientific Reports2045-23222020-09-011011910.1038/s41598-020-73085-1Distinct lung microbiota associate with HIV-associated chronic lung disease in childrenSudha Bhadriraju0Douglas W. Fadrosh1Meera K. Shenoy2Din L. Lin3Kole V. Lynch4Kathryn McCauley5Rashida A. Ferrand6Edith D. Majonga7Grace McHugh8Laurence Huang9Susan V. Lynch10John Z. Metcalfe11Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital and Trauma Center, University of California San FranciscoDivision of Gastroenterology, Department of Medicine, University of CaliforniaDivision of Gastroenterology, Department of Medicine, University of CaliforniaDivision of Gastroenterology, Department of Medicine, University of CaliforniaDivision of Gastroenterology, Department of Medicine, University of CaliforniaDivision of Gastroenterology, Department of Medicine, University of CaliforniaBiomedical Research and Training InstituteBiomedical Research and Training InstituteBiomedical Research and Training InstituteDivision of Pulmonary and Critical Care Medicine, San Francisco General Hospital and Trauma Center, University of California San FranciscoDivision of Gastroenterology, Department of Medicine, University of CaliforniaDivision of Pulmonary and Critical Care Medicine, San Francisco General Hospital and Trauma Center, University of California San FranciscoAbstract Chronic lung disease (CLD) is a common co-morbidity for HIV-positive children and adolescents on antiretroviral therapy (ART) in sub-Saharan Africa. In this population, distinct airway microbiota may differentially confer risk of CLD. In a cross-sectional study of 202 HIV-infected children aged 6–16 years in Harare, Zimbabwe, we determined the association of sputum microbiota composition (using 16S ribosomal RNA V4 gene region sequencing) with CLD defined using clinical, spirometric, or radiographic criteria. Forty-two percent of children were determined to have CLD according to our definition. Dirichlet multinomial mixtures identified four compositionally distinct sputum microbiota structures. Patients whose sputum microbiota was dominated by Haemophilus, Moraxella or Neisseria (HMN) were at 1.5 times higher risk of CLD than those with Streptococcus or Prevotella (SP)-dominated microbiota (RR = 1.48, p = 0.035). Cell-free products of HMN sputum microbiota induced features of epithelial disruption and inflammatory gene expression in vitro, indicating enhanced pathogenic potential of these CLD-associated microbiota. Thus, HIV-positive children harbor distinct sputum microbiota, with those dominated by Haemophilus, Moraxella or Neisseria associated with enhanced pathogenesis in vitro and clinical CLD.https://doi.org/10.1038/s41598-020-73085-1
spellingShingle Sudha Bhadriraju
Douglas W. Fadrosh
Meera K. Shenoy
Din L. Lin
Kole V. Lynch
Kathryn McCauley
Rashida A. Ferrand
Edith D. Majonga
Grace McHugh
Laurence Huang
Susan V. Lynch
John Z. Metcalfe
Distinct lung microbiota associate with HIV-associated chronic lung disease in children
Scientific Reports
title Distinct lung microbiota associate with HIV-associated chronic lung disease in children
title_full Distinct lung microbiota associate with HIV-associated chronic lung disease in children
title_fullStr Distinct lung microbiota associate with HIV-associated chronic lung disease in children
title_full_unstemmed Distinct lung microbiota associate with HIV-associated chronic lung disease in children
title_short Distinct lung microbiota associate with HIV-associated chronic lung disease in children
title_sort distinct lung microbiota associate with hiv associated chronic lung disease in children
url https://doi.org/10.1038/s41598-020-73085-1
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