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The respiratory and gut microbiota in pulmonary tuberculosis
Thesis (PhD)--Stellenbosch University, 2024.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : Stellenbosch University
2025
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| _version_ | 1867614101446852608 |
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| access_status_str | Open Access |
| author | Chiyaka, Tinaye Leon |
| author2 | Theron, Grant |
| author_browse | Chiyaka, Tinaye Leon Theron, Grant |
| author_facet | Theron, Grant Chiyaka, Tinaye Leon |
| author_sort | Chiyaka, Tinaye Leon |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description |
Thesis (PhD)--Stellenbosch University, 2024. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/131617 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:46:41.344Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/131617 The respiratory and gut microbiota in pulmonary tuberculosis Chiyaka, Tinaye Leon Theron, Grant Naidoo, Charissa Moodley, Suventha Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Respiratory organs -- Microbiology Tuberculosis -- Microbiology -- South Africa Intestines -- Microbiology -- South Africa Human body -- Microbiology -- South Africa UCTD Thesis (PhD)--Stellenbosch University, 2024. ENGLISH ABSTRACT: Background: Tuberculosis (TB) is a public health crisis and one of the highest causes of mortality in South Africa. The human microbiota modulates the immune system via metabolites like short chain fatty acids (SCFAs) and may play a role in TB pathogenesis, potentially serving as a therapeutic target. Hypotheses: At different stages of the TB spectrum (latent, active and post-treatment), the microbiota at different sites of the body (respiratory including aerosol, gut) will vary. Furthermore, non-invasive respiratory specimens (aerosols) are, in addition to having diagnostic potential, reflective of the lung microbiota. Methods: We enrolled participants from different cohorts across the spectrum of TB disease including people living with HIV (PLHIV) resistant to Mycobacterium tuberculosis (Mtb) infection (resisters), PLHIV with latent TB infection (LTBI), pre-treatment active TB, people with a history of TB (PHTBs) and healthy controls including household contacts (HHCs). Depending on the cohort, we collected upper respiratory tract (URT; oral wash, oro- and naso- swabs, supraglottic fluid), sputum, lower respiratory tract [LRT; aerosols, bronchoalveolar lavage (BALF), protected specimen brushings (PSBs)] or stool specimens (spirometry also done in PHTBs). Microbial DNA from these specimens underwent 16S rRNA sequencing and was analysed alongside clinical and microbiological meta-data. Results: In Chapter 2, we compared respiratory and gut microbiota between resisters to LTBIs and showed resisters have 1) similar URT and sputum microbial diversity but commensal anaerobe enrichment, 2) less diverse LRT microbiota, and 3) gut microbiota enriched with butyrate-producing anaerobes, when compared to LTBI. Our data demonstrates resisters have an apparent healthy microbiota compared to people with LTBI and suggest microbial dysbiosis may precede incident active TB. Chapter 3 evaluated the respiratory microbiota of people with active TB and compared, within these people, involved (diseased) versus uninvolved (non-diseased) contralateral lung lobes. Additionally, these lobes were compared to those of healthy controls. We show 1) the LRT in people with active TB is less diverse with Methylobacterium mesophilicum, Moraxella ovis and Mtb-enrichment compared to their URT and sputum, 2) involved lobes have similar diversity to uninvolved lobes but M. ovis-enriched, and 3) both involved and uninvolved lobes of people with TB are oral anaerobe-depleted vs. healthy controls. This demonstrates the microbiota in the lower airways of people with TB is less diverse than the upper airways and sputum. Furthermore, site-of-disease lung lobes are less diverse, Mtb-enriched and oral anaerobe-depleted vs. healthy lung lobes. Antibiotic therapy for TB alters microbiota, but period of recovery of the microbiota post-treatment is under characterised. Chapter 4 evaluates microbiota of PHTBs one-, two-, three-, four-, or five-years (Y1-5) post-treatment, comparing them to healthy household contacts (HHCs). We show 1) PHTBs sputum and gut microbiota diversity metrics recover post-treatment and are comparable to HHCs with no TB history but sputum of PHTBs remained enriched with pathobionts (Alloiococcus, Moraxella), and 2) PHTBs with abnormal lung function are, compared to PHTBs with normal lung function, have sputum enriched with taxa typically associated with active TB (Haemophilus, Megasphaera) In summary, we showed the sputum and gut microbiota of PHTBs recovers by Y1 and is comparable to people with no history of TB but levels of taxa associated with respiratory infections are elevated. Finally, in Chapter 5 we evaluated whether aerosols collected by the Pneumonia Check (PMC) device can be used as alternative specimen for TB diagnosis using the Xpert MTB/RIF Ultra (Ultra) test, as well as studying the lung microbiota, which requires invasive sampling. We showed 1) MTBC is detectable by Ultra in aerosols in ~57% of TB-positive patients, 2) aerosols are compositionally distinct to sputum, oral washes and BALF and 3) aerosols sequencing data better captures presence of Mycobacterium than sputum. These data show PMC-captured aerosol can be used for diagnosis and aerosols more accurately reflect lung microbes than to sputum and can be used as a proxy to study the site-of-disease lung microbiota. Conclusion: This body of work collectively provides a comprehensive overview on microbiota in TB at various stages of the disease. This work lays a foundation for future work design and evaluations that can target microbiota to avert poor clinical outcomes in TB. AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar. Doctoral 2025-01-29T10:21:54Z 2025-01-29T10:21:54Z 2024-12 Thesis https://scholar.sun.ac.za/handle/10019.1/131617 en Stellenbosch University xxiii, 225 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Respiratory organs -- Microbiology Tuberculosis -- Microbiology -- South Africa Intestines -- Microbiology -- South Africa Human body -- Microbiology -- South Africa UCTD Chiyaka, Tinaye Leon The respiratory and gut microbiota in pulmonary tuberculosis |
| title | The respiratory and gut microbiota in pulmonary tuberculosis |
| title_full | The respiratory and gut microbiota in pulmonary tuberculosis |
| title_fullStr | The respiratory and gut microbiota in pulmonary tuberculosis |
| title_full_unstemmed | The respiratory and gut microbiota in pulmonary tuberculosis |
| title_short | The respiratory and gut microbiota in pulmonary tuberculosis |
| title_sort | respiratory and gut microbiota in pulmonary tuberculosis |
| topic | Respiratory organs -- Microbiology Tuberculosis -- Microbiology -- South Africa Intestines -- Microbiology -- South Africa Human body -- Microbiology -- South Africa UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/131617 |
| work_keys_str_mv | AT chiyakatinayeleon therespiratoryandgutmicrobiotainpulmonarytuberculosis AT chiyakatinayeleon respiratoryandgutmicrobiotainpulmonarytuberculosis |