TB - TuberculosisTB-LUNGNCT04700579
Pre- and Post-treatment Lung Microbiota, Metabolome and Immune Signatures at the Site of Disease in Patients With Active Pulmonary Tuberculosis
An observational study of TB - Tuberculosis and HIV/AIDS, run by University of Stellenbosch at 3 sites in South Africa.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- TB - Tuberculosis, HIV/AIDS
- How many people
- 150 participants
- Where
- 3 sitesSouth Africa
- Study dates
- 4 Mar 2021to 31 Dec 2027
- How long will I take part?
- 18 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
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.
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 11Show fewer
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
South Africa3 sites, 3 recruiting
- Recruiting
Kraaifontein Community Health Centre
Cape Town, Western Cape, 7570
Grant Theron, PhD, (+27) 21 938 9693 ext. 9693, gtheron@sun.ac.za
Tinaye Chiyaka, PhD, (+27) 21 938 9954 ext. 9954, tinayechiyaka@sun.ac.za
- Recruiting
Scottsdene Clinic
Cape Town, Western Cape, 7570
Grant Theron, PhD, (+27) 21 938 9693 ext. 9693, gtheron@sun.ac.za
Tinaye Chiyaka, PhD, (+27) 21 938 9954 ext. 9954, tinayechiyaka@sun.ac.za
- Recruiting
Wallacedene Clinic
Cape Town, Western Cape, 7570
Grant Theron, PhD, (+27) 21 938 9693 ext. 9693, gtheron@sun.ac.za
Tinaye WP Chiyaka, PhD, (+27) 21 938 9954 ext. 9954, tinayechiyaka@sun.ac.za
About this study
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.
Read the 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.
- Conditions
- TB - Tuberculosis, HIV/AIDS
- Keywords
- Microbiome, Short Chain Fatty Acids, Immunological Biomarkers
- Medical subject headings
- Latent Tuberculosis, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 18 months
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.
Measured: Up to 18 months
Evaluate the impact of treatment on the lung microbiome.
Characterize bacterial community resilience alongside changes in microbial and host biomarkers.
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2021
- Study start4 Mar 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for TB - TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
- Target duration
- 18 Months
Sponsor and investigators
- Lead sponsor
- University of Stellenbosch
- Sponsor type
- University, hospital or other
- Collaborators
- New York University
- Responsible party
- Principal investigator, Grant Theron, University of Stellenbosch
- Investigators
- Grant Theron, PhD, Principal investigator, University of Stellenbosch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04700579
- Sponsor's protocol ID
- N19/09/126
- Acronym
- TB-LUNG
- Status last verified
- Apr 2026
- First submitted
- 28 Dec 2020
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI. Human gut microbiome viewed across age and geography. Nature. 2012 May 9;486(7402):222-7. doi: 10.1038/nature11053.
PubMed 22699611Wade WG. The oral microbiome in health and disease. Pharmacol Res. 2013 Mar;69(1):137-43. doi: 10.1016/j.phrs.2012.11.006. Epub 2012 Nov 28.
PubMed 23201354Weiner J 3rd, Parida SK, Maertzdorf J, Black GF, Repsilber D, Telaar A, Mohney RP, Arndt-Sullivan C, Ganoza CA, Fae KC, Walzl G, Kaufmann SH. Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients. PLoS One. 2012;7(7):e40221. doi: 10.1371/journal.pone.0040221. Epub 2012 Jul 23.
PubMed 22844400Grice EA, Kong HH, Renaud G, Young AC; NISC Comparative Sequencing Program; Bouffard GG, Blakesley RW, Wolfsberg TG, Turner ML, Segre JA. A diversity profile of the human skin microbiota. Genome Res. 2008 Jul;18(7):1043-50. doi: 10.1101/gr.075549.107. Epub 2008 May 23.
PubMed 18502944Shenoy MK, Iwai S, Lin DL, Worodria W, Ayakaka I, Byanyima P, Kaswabuli S, Fong S, Stone S, Chang E, Davis JL, Faruqi AA, Segal MR, Huang L, Lynch SV. Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in Patients with HIV and Pneumonia. Am J Respir Crit Care Med. 2017 Jan 1;195(1):104-114. doi: 10.1164/rccm.201603-0523OC.
PubMed 27447987Wipperman MF, Fitzgerald DW, Juste MAJ, Taur Y, Namasivayam S, Sher A, Bean JM, Bucci V, Glickman MS. Antibiotic treatment for Tuberculosis induces a profound dysbiosis of the microbiome that persists long after therapy is completed. Sci Rep. 2017 Sep 7;7(1):10767. doi: 10.1038/s41598-017-10346-6.
PubMed 28883399Botero LE, Delgado-Serrano L, Cepeda ML, Bustos JR, Anzola JM, Del Portillo P, Robledo J, Zambrano MM. Respiratory tract clinical sample selection for microbiota analysis in patients with pulmonary tuberculosis. Microbiome. 2014 Aug 25;2:29. doi: 10.1186/2049-2618-2-29. eCollection 2014.
PubMed 25225609Cheung MK, Lam WY, Fung WY, Law PT, Au CH, Nong W, Kam KM, Kwan HS, Tsui SK. Sputum microbiota in tuberculosis as revealed by 16S rRNA pyrosequencing. PLoS One. 2013;8(1):e54574. doi: 10.1371/journal.pone.0054574. Epub 2013 Jan 24.
PubMed 23365674Cui Z, Zhou Y, Li H, Zhang Y, Zhang S, Tang S, Guo X. Complex sputum microbial composition in patients with pulmonary tuberculosis. BMC Microbiol. 2012 Nov 23;12:276. doi: 10.1186/1471-2180-12-276.
PubMed 23176186Segal LN, Clemente JC, Tsay JC, Koralov SB, Keller BC, Wu BG, Li Y, Shen N, Ghedin E, Morris A, Diaz P, Huang L, Wikoff WR, Ubeda C, Artacho A, Rom WN, Sterman DH, Collman RG, Blaser MJ, Weiden MD. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat Microbiol. 2016 Apr 4;1:16031. doi: 10.1038/nmicrobiol.2016.31.
PubMed 27572644Segal LN, Alekseyenko AV, Clemente JC, Kulkarni R, Wu B, Gao Z, Chen H, Berger KI, Goldring RM, Rom WN, Blaser MJ, Weiden MD. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome. 2013 Jul 1;1(1):19. doi: 10.1186/2049-2618-1-19.
PubMed 24450871Naidoo CC, Nyawo GR, Wu BG, Walzl G, Warren RM, Segal LN, Theron G. The microbiome and tuberculosis: state of the art, potential applications, and defining the clinical research agenda. Lancet Respir Med. 2019 Oct;7(10):892-906. doi: 10.1016/S2213-2600(18)30501-0. Epub 2019 Mar 22.
PubMed 30910543
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre- and Post-treatment Lung Microbiota, Metabolome and Immune Signatures at the Site of Disease in Patients With Active Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT04700579
- Acronym / sponsor ID
- TB-LUNG / N19/09/126
- Conditions
- TB - Tuberculosis, HIV/AIDS
- Keywords
- Microbiome, Short Chain Fatty Acids, Immunological Biomarkers
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- University of StellenboschUniversity, hospital or other
- Collaborators
- New York University
- Study start
- 4 Mar 2021 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 8 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 18 Months
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Background: PubMed 22699611Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI. Human gut microbiome viewed across age and geography. Nature. 2012 May 9;486(7402):222-7. doi: 10.1038/nature11053.
- Background: PubMed 23201354Wade WG. The oral microbiome in health and disease. Pharmacol Res. 2013 Mar;69(1):137-43. doi: 10.1016/j.phrs.2012.11.006. Epub 2012 Nov 28.
- Background: PubMed 22844400Weiner J 3rd, Parida SK, Maertzdorf J, Black GF, Repsilber D, Telaar A, Mohney RP, Arndt-Sullivan C, Ganoza CA, Fae KC, Walzl G, Kaufmann SH. Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients. PLoS One. 2012;7(7):e40221. doi: 10.1371/journal.pone.0040221. Epub 2012 Jul 23.
- Background: PubMed 18502944Grice EA, Kong HH, Renaud G, Young AC; NISC Comparative Sequencing Program; Bouffard GG, Blakesley RW, Wolfsberg TG, Turner ML, Segre JA. A diversity profile of the human skin microbiota. Genome Res. 2008 Jul;18(7):1043-50. doi: 10.1101/gr.075549.107. Epub 2008 May 23.
- Background: PubMed 27447987Shenoy MK, Iwai S, Lin DL, Worodria W, Ayakaka I, Byanyima P, Kaswabuli S, Fong S, Stone S, Chang E, Davis JL, Faruqi AA, Segal MR, Huang L, Lynch SV. Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in Patients with HIV and Pneumonia. Am J Respir Crit Care Med. 2017 Jan 1;195(1):104-114. doi: 10.1164/rccm.201603-0523OC.
- Background: PubMed 28883399Wipperman MF, Fitzgerald DW, Juste MAJ, Taur Y, Namasivayam S, Sher A, Bean JM, Bucci V, Glickman MS. Antibiotic treatment for Tuberculosis induces a profound dysbiosis of the microbiome that persists long after therapy is completed. Sci Rep. 2017 Sep 7;7(1):10767. doi: 10.1038/s41598-017-10346-6.
- Background: PubMed 25225609Botero LE, Delgado-Serrano L, Cepeda ML, Bustos JR, Anzola JM, Del Portillo P, Robledo J, Zambrano MM. Respiratory tract clinical sample selection for microbiota analysis in patients with pulmonary tuberculosis. Microbiome. 2014 Aug 25;2:29. doi: 10.1186/2049-2618-2-29. eCollection 2014.
- Background: PubMed 23365674Cheung MK, Lam WY, Fung WY, Law PT, Au CH, Nong W, Kam KM, Kwan HS, Tsui SK. Sputum microbiota in tuberculosis as revealed by 16S rRNA pyrosequencing. PLoS One. 2013;8(1):e54574. doi: 10.1371/journal.pone.0054574. Epub 2013 Jan 24.
- Background: PubMed 23176186Cui Z, Zhou Y, Li H, Zhang Y, Zhang S, Tang S, Guo X. Complex sputum microbial composition in patients with pulmonary tuberculosis. BMC Microbiol. 2012 Nov 23;12:276. doi: 10.1186/1471-2180-12-276.
- Background: PubMed 27572644Segal LN, Clemente JC, Tsay JC, Koralov SB, Keller BC, Wu BG, Li Y, Shen N, Ghedin E, Morris A, Diaz P, Huang L, Wikoff WR, Ubeda C, Artacho A, Rom WN, Sterman DH, Collman RG, Blaser MJ, Weiden MD. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat Microbiol. 2016 Apr 4;1:16031. doi: 10.1038/nmicrobiol.2016.31.
- Background: PubMed 24450871Segal LN, Alekseyenko AV, Clemente JC, Kulkarni R, Wu B, Gao Z, Chen H, Berger KI, Goldring RM, Rom WN, Blaser MJ, Weiden MD. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome. 2013 Jul 1;1(1):19. doi: 10.1186/2049-2618-1-19.
- Background: PubMed 30910543Naidoo CC, Nyawo GR, Wu BG, Walzl G, Warren RM, Segal LN, Theron G. The microbiome and tuberculosis: state of the art, potential applications, and defining the clinical research agenda. Lancet Respir Med. 2019 Oct;7(10):892-906. doi: 10.1016/S2213-2600(18)30501-0. Epub 2019 Mar 22.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Grant Theron, PhD principal investigator
University of Stellenbosch
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of TB - Tuberculosis and HIV/AIDS, run by University of Stellenbosch at 3 sites in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Grant Theron, PhD ((+27) 021 938 9693, gtheron@sun.ac.za), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterization of changes in microbiota in diseased vs. non-diseased lung segments, stratified by HIV status. (time frame: Up to 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04700579, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.