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Project Topic
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The microbiota/microbiome, complex communities of microbes in mammals, play a significant role in health and disease including induction/function of the immune system. However, baseline information on their composition and potential role(s) in pulmonary tuberculosis (TB) in sub-Saharan Africa, is lacking. The overall purpose of this proposal is to determine the microbiome composition in pulmonary TB in Kampala Uganda, and examine its relationship with treatment- and immune-response in TB patients relative to their household healthy contacts without TB-infection and HIV-infection. In context of treatment naïve adult TB patients in Kampala Uganda, two specific aims are contingent to this goal; Specific Aims 1. a) To examine the relationship between sputum and gut microbiome diversity and disease. b) To investigate the relationship between sputum and gut microbiome composition and treatment response among patients on first-line TB therapy, and whether dysbiosis resolves in patients who get cured from TB after successfully completing anti-TB therapy. 2. To investigate the relationship between sputum and gut microbiome composition and inflammatory cytokine production capacity. Study design and approach This will be a longitudinal study nested in a concurrent MTI-project at Mulago National Referral Hospital in Kampala Uganda, which maintains a cohort of 320 Xpert-positive, treatment-naïve adult TB patients with followup at months 2, 5, 12, 18 and 24. We will investigate sputum, stool and blood samples from 160 participants (purposive sampling) at baseline (day 0) and months 2, 5, 12, 18 & 24 for microbial and cytokine profiles. Of the 160 participants, 100 will be pulmonary TB cases randomly selected from the parent MTI-cohort of whom 50 will be HIV-positive (TB+/HIV+) and 50 HIV-negative (TB+/HIV). Also, we will similarly investigate 60 household contacts as the comparator group (controls). Household contacts will be TB-negative family members of the 100 TB cases, of whom one half (30) will be HIV-positive without respiratory/pulmonary symptoms based on interferon-γ release assay (i.e. HIV+/TB- sub-group) while the other half (30) will be both HIV-negative and TBnegative i.e. the healthy contacts (HIV-/TB-). On achieving our aims, we will provide human microbiota profiles from a TB-endemic/HIV-burden setting, which profiles could be used as a reference for other settings in sub-Saharan Africa. Also, our data might reveal potential markers of TB-treatment response or failure. Such information is vital in devising novel region- or country-specific interventions.
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