Pre- and Post-treatment Lung Microbiota, Metabolome and Immune Signatures at the Site of Disease in Patients With Active Pulmonary Tuberculosis (TB-LUNG)

April 29, 2026 updated by: Grant Theron, University of Stellenbosch
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.

Study Overview

Status

Recruiting

Conditions

Detailed Description

The human body is host to complex microbial communities at different anatomical sites such as the gut, oral cavity, vagina, skin, and the lower respiratory tract - a site previously thought to be sterile. Growing evidence has implicated the role of the human microbiome in various diseases for example, Prevotella-enriched lung communities in HIV-positive pneumonia patients independently predict 70-day mortality, and Lactobacillus enriched murine gut microbiome alleviates asthma-like symptoms. However, despite the scale and severity of TB, there are limited studies on the microbiome in TB cases, the site of disease, and the effect of treatment, especially in the context of HIV. These key knowledge gaps preclude the design and evaluation of interventions that could target the microbiome and avert poor treatment outcomes in TB.

To date the few microbiome studies in TB have focused on the upper respiratory tract (using specimens such as sputum) and gut rather than the site of disease which, in TB, is typically the lung. These studies have shown associations between the microbiome and state of disease. For example, mice colonized with Helicobacter hepaticus in the gut demonstrate poor control of mycobacterial growth, heightened inflammation, and severe tissue pathology in the lungs. The lung which is the site of disease in pulmonary TB has been widely considered sterile until recently and the lung microbiome remains widely understudied in TB regardless of the potential impact it might have in TB pathogenesis. One of the major reasons why the lung is understudied is the difficult in sampling the lung. The investigators will implement a modified bronchoscopy procedure to avoid microbial cross-contamination from neighbouring anatomical sites (including from diseased to healthy parts of the lungs) and to accurately sample the low biomass in the bronchoalveolar space. The investigators hypothesize that TB cases have a distinct site-of-disease lung microbiota compared to non-diseased contralateral tissue, characterized by an enrichment of oral anaerobic fermenters, SCFAs, and impaired inflammation and tissue repair biomarkers. They also expect microbial and host biomarkers to be altered by TB treatment. A study by one of the investigators has already demonstrated lung microbiomes enriched with anaerobic oral taxa are associated with lung inflammation of the Th17 phenotype. The products of microbial anaerobic metabolism have also been shown to modulate immune response to diseases. The investigators will correlate the complex microbial communities at the site-of-disease in TB with the microbial and host biomarkers at the site-of-disease.

The study will recruit self-reporting patients with their first TB episode and Xpert MTB/RIF Ultra-confirmed TB from Scottsdene and Wallacedene primary care clinics in Cape Town. A total of 50 TB cases equally stratified by HIV status and 50 healthy household contacts (HHC) also stratified by HIV will be recruited. In addition to HIV-negatives, the study is recruiting an equal number of ART-treated HIV-positive TB cases, because there an epidemiologically important subpopulation with impaired pulmonary immunity. An additional 50 sick controls with other pulmonary diseases (Asthma, Chronic obstructive pulmonary disease (COPD), Cancer, Bronchiectasis (including post-TB) and Pneumonia) will recruited as comparator groups.

Study Type

Observational

Enrollment (Estimated)

150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • South Africa
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7570
        • Recruiting
        • Kraaifontein Community Health Centre
        • Contact:
        • Contact:
      • Cape Town, Western Cape, South Africa, 7570
        • Recruiting
        • Scottsdene Clinic
        • Contact:
        • Contact:
      • Cape Town, Western Cape, South Africa, 7570
        • Recruiting
        • Wallacedene Clinic
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

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.

Description

Inclusion Criteria:

  • 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.
  • Willing to undergo a research bronchoscopy at baseline, 6 months and 18 months and likely to remain in the area for the study period.
  • If HIV-positive, must be stable on antiretroviral therapy (ART) for ≥1 year.
  • Able and willing to return for follow-up visits, with no plans to move in the near future.
  • Willing to comply with study requirements i.e. provision of contact details and written, informed consent prior to enrolment.

Exclusion Criteria:

  • Less than 18 years or older than 60 years of age.
  • Has already initiated TB treatment.
  • Rifampicin resistant.
  • Has a previous history of TB.
  • Bilateral TB disease defined as both lungs with extensive TB disease
  • Has received probiotics, antibiotics or inhaled steroids within three months prior to enrolment (not applicable to sick controls)
  • Has diabetes mellitus, which affects TB disease, treatment response, and the microbiome
  • Has a contraindication for bronchoscopy (e.g., FEV1 <70%), as determined by bronchoscopists according to best practice guidelines
  • Has a daily alcohol intake of more than 6 beers or 4 mixed drinks
  • Is pregnant (a commercial human chorionic gonadotropin determination assay will be performed in accordance with manufacturer's guidance on urine) or pregnancy planned for follow-up period
  • Recent hospitalization for any reason

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
TB Cases
  • n= 50 (25 HIV positive and 25 HIV negative)
  • Xpert MTB/RIF Ultra-confirmed TB
Healthy Household Contacts
  • n= (25 HIV positive and 25 HIV negative)
  • Culture negative TB result
Sick controls
  • n=50
  • Diseases: Asthma, Chronic obstructive pulmonary disease (COPD), Cancer, Bronchiectasis (including post-TB) and Pneumonia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterization of changes in microbiota in diseased vs. non-diseased lung segments, stratified by HIV status.
Time Frame: Up to 18 months
Lung microbiome in diseased and non-diseased segments determined by 16S rRNA gene sequencing.
Up to 18 months
Association of specific microbial taxa in diseased segments with elevated SCFAs and impaired host inflammation and tissue repair biomarkers.
Time Frame: Up to 18 months
Correlation analysis of specific cytokines profiled using commercial multiplexed Luminex panels and SCFAs measured using Gas chromatography-mass spectrometry (GC-MS) assays.
Up to 18 months
Evaluate the impact of treatment on the lung microbiome.
Time Frame: Up to 18 months
Characterize bacterial community resilience alongside changes in microbial and host biomarkers.
Up to 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Stellenbosch

Collaborators

New York University

Investigators

  • Principal Investigator: Grant Theron, PhD, University of Stellenbosch

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2021

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

December 28, 2020

First Submitted That Met QC Criteria

January 6, 2021

First Posted (Actual)

January 8, 2021

Study Record Updates

Last Update Posted (Actual)

May 6, 2026

Last Update Submitted That Met QC Criteria

April 29, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • N19/09/126

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Collaborators will have access to de-identified IPD data. Other researchers wishing to access the data will be required to sign a data sharing agreement as per institutional policies.

IPD Sharing Time Frame

The data will be available once the findings are published.

IPD Sharing Access Criteria

Data access will be granted to interested collaborators and parties through sharing of data files or login information for the study's secure RedCap electronic database during the course of patient recruitment.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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