More than Mycobacterium tuberculosis: site-of-disease microbial communities, and their functional and clinical profiles in tuberculous lymphadenitis.

Autor: Nyawo GR; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa.; African Microbiome Institute, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa., Naidoo CC; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa.; African Microbiome Institute, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa., Wu B; Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA., Sulaiman I; Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA., Clemente JC; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Li Y; Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA., Minnies S; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa., Reeve BWP; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa., Moodley S; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa.; African Microbiome Institute, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa., Rautenbach C; National Health Laboratory Service, Tygerberg Hospital, Cape Town, Western Cape, South Africa.; Division of Medical Microbiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa., Wright C; Division Anatomical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa., Singh S; Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA., Whitelaw A; National Health Laboratory Service, Tygerberg Hospital, Cape Town, Western Cape, South Africa.; Division of Medical Microbiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa., Schubert P; National Health Laboratory Service, Tygerberg Hospital, Cape Town, Western Cape, South Africa.; Division Anatomical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa., Warren R; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa., Segal L; Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA., Theron G; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa gtheron@sun.ac.za.; African Microbiome Institute, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa.
Jazyk: angličtina
Zdroj: Thorax [Thorax] 2023 Mar; Vol. 78 (3), pp. 297-308. Date of Electronic Publication: 2022 Dec 08.
DOI: 10.1136/thorax-2022-219103
Abstrakt: Background: Lymphadenitis is the most common extrapulmonary tuberculosis (EPTB) manifestation. The microbiome is important to human health but uninvestigated in EPTB. We profiled the site-of-disease lymph node microbiome in tuberculosis lymphadenitis (TBL).
Methods: Fine-needle aspiration biopsies were collected from 158 pretreatment presumptive TBL patients in Cape Town, South Africa. 16S Illumina MiSeq rRNA gene sequencing was done.
Results: We analysed 89 definite TBLs (dTBLs) and 61 non-TBLs (nTBLs), which had similar α- but different β-diversities (p= 0.001 ). Clustering identified five lymphotypes prior to TB status stratification: Mycobacterium- dominant , Prevotella- dominant and Streptococcus- dominant lymphotypes were more frequent in dTBLs whereas a Corynebacterium -dominant lymphotype and a fifth lymphotype (no dominant taxon) were more frequent in nTBLs. When restricted to dTBLs, clustering identified a Mycobacterium -dominant lymphotype with low α-diversity and non- Mycobacterium -dominated lymphotypes (termed Prevotella-Corynebacterium , Prevotella-Streptococcus ). The Mycobacterium dTBL lymphotype was associated with HIV-positivity and features characteristic of severe lymphadenitis (eg, larger nodes). dTBL microbial communities were enriched with potentially proinflammatory microbial short-chain fatty acid metabolic pathways (propanoate, butanoate) vs nTBLs. 11% (7/61) of nTBLs had Mycobacterium reads BLAST-confirmed as Mycobacterium tuberculosis complex.
Conclusions: TBL at the site-of-disease is not microbially homogeneous. Distinct microbial community clusters exist that, in our setting, are associated with different clinical characteristics, and immunomodulatory potentials. Non- Mycobacterium -dominated dTBL lymphotypes, which contain taxa potentially targeted by TB treatment, were associated with milder, potentially earlier stage disease. These investigations lay foundations for studying the microbiome's role in lymphatic TB. The long-term clinical significance of these lymphotypes requires prospective validation.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze: MEDLINE