Distinct lung microbiota associate with HIV-associated chronic lung disease in children
Sudha Bhadriraju1, Douglas W Fadrosh2, Meera K Shenoy2
1Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital and Trauma Center, University of California San Francisco, 1001 Potrero Avenue, Rm 5K1, San Francisco, CA, 94110-0111, USA.
Insights
HIV-positive children with chronic lung disease (CLD) often have distinct airway bacteria. Sputum dominated by Haemophilus, Moraxella, or Neisseria increases CLD risk and shows greater pathogenic potential.
Area of Science:
- Microbiology
- Pulmonology
- Infectious Diseases
Background:
- Chronic lung disease (CLD) is a frequent comorbidity in HIV-infected children on antiretroviral therapy (ART) in sub-Saharan Africa.
- Distinct airway microbiota compositions may influence CLD risk in this vulnerable population.
Purpose of the Study:
- To investigate the association between sputum microbiota composition and CLD in HIV-infected children.
- To explore the pathogenic potential of CLD-associated airway bacteria.
Main Methods:
- Cross-sectional study of 202 HIV-infected children (aged 6-16 years) in Harare, Zimbabwe.
- Sputum microbiota composition analyzed using 16S ribosomal RNA V4 gene sequencing.
- CLD defined by clinical, spirometric, or radiographic criteria.
Main Results:
- 42% of children had CLD.
- Four distinct sputum microbiota structures were identified.
- Microbiota dominated by Haemophilus, Moraxella, or Neisseria (HMN) showed a 1.5-fold increased risk of CLD compared to Streptococcus/Prevotella (SP)-dominated microbiota (RR=1.48, p=0.035).
- In vitro, cell-free products from HMN microbiota induced epithelial disruption and inflammatory gene expression.
Conclusions:
- HIV-positive children exhibit distinct sputum microbiota profiles.
- HMN-dominated microbiota are associated with increased CLD risk and enhanced in vitro pathogenesis.
- Targeting specific airway bacteria may offer novel therapeutic strategies for CLD in HIV-infected 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 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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