The diverse microbial communities in different parts of the human body (microbiome) are important for health but understudied in pulmonary tuberculosis (TB), which is the single biggest infectious cause of death in the world. The investigators will study the site-of-disease microbiome (in the lung bronchoalveolar space) in TB cases to investigate how, before TB treatment, metabolic compounds made by microbes affect host biomarkers important for TB control. The investigators will ask this question again at the end-of-treatment and one year later. Specifically, the investigators will sample the lung at the active TB hotspot identified by imaging and compare this to a non-involved lung segment usually in the opposite lung. The investigators will compare the lung microbiome to other sites in the body (i.e. oral cavity, nasopharynx, supraglottis, and gut). A small amount of blood (\~15 ml) will be collected to assess peripheral immunological correlates of the host microbiome. Protected specimen brushings of the lung will be used to explore transcriptomic signatures and how these relate to the lung microbiome. The investigators will also apply these questions to the same number of controls (healthy patients and patients with an alternative diagnoses). This will lay the foundation for clinical trials to evaluate if specific bacteria have diagnostic (e.g., PCR) or therapeutic potential (e.g., antibiotics, prebiotics, probiotics, vaccines) where targeting the microbiome could improve clinical outcomes.
18-60 years old.
Agree to undergo CXR and/or CT scan.
Has unilateral TB disease defined as one lung with extensive evidence of TB disease (non-applicable to healthy controls; sick controls will require an alternative diagnosis).
No evidence of prior TB treatment and/or CXR/CT does not have obvious evidence of prior TB.
Less than 18 years or older than 60 years of age.
Has already initiated TB treatment.
Rifampicin resistant.
Has a previous history of TB.
Self-presenting patients with Xpert MTB/RIF Ultra-confirmed TB (n=50, equally stratified by HIV) and culture negative HHCs (n=50, equally stratified by HIV) will be recruited from primary care clinics (Scottsdene and Wallacedene) in Cape Town, South Africa. An additional 50 sick controls with other lung diseases will be referred from Tygerberg Academic Hospital.
Cohort
Prospective
Not listed
Characterization of changes in microbiota in diseased vs. non-diseased lung segments, stratified by HIV status.
Lung microbiome in diseased and non-diseased segments determined by 16S rRNA gene sequencing.
Association of specific microbial taxa in diseased segments with elevated SCFAs and impaired host inflammation and tissue repair biomarkers.
Correlation analysis of specific cytokines profiled using commercial multiplexed Luminex panels and SCFAs measured using Gas chromatography-mass spectrometry (GC-MS) assays.
Evaluate the impact of treatment on the lung microbiome.
Characterize bacterial community resilience alongside changes in microbial and host biomarkers.
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University of Stellenbosch
Lead sponsor
New York University
Collaborator
