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The Sputum Microbiome in Pulmonary Tuberculosis and Its Association With Disease Manifestations: A Cross-Sectional Study

Each day, approximately 27,000 people become ill with tuberculosis (TB), and 4,000 die from this disease. Pulmonary TB is the main clinical form of TB, and affects the lungs with a considerably heterogeneous manifestation among patients. Immunomodulation by an interplay of host-, environment-, and p...

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Autores principales: Ticlla, Monica R., Hella, Jerry, Hiza, Hellen, Sasamalo, Mohamed, Mhimbira, Francis, Rutaihwa, Liliana K., Droz, Sara, Schaller, Sarah, Reither, Klaus, Hilty, Markus, Comas, Inaki, Beisel, Christian, Schmid, Christoph D., Fenner, Lukas, Gagneux, Sebastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417804/
https://www.ncbi.nlm.nih.gov/pubmed/34489876
http://dx.doi.org/10.3389/fmicb.2021.633396
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author Ticlla, Monica R.
Hella, Jerry
Hiza, Hellen
Sasamalo, Mohamed
Mhimbira, Francis
Rutaihwa, Liliana K.
Droz, Sara
Schaller, Sarah
Reither, Klaus
Hilty, Markus
Comas, Inaki
Beisel, Christian
Schmid, Christoph D.
Fenner, Lukas
Gagneux, Sebastien
author_facet Ticlla, Monica R.
Hella, Jerry
Hiza, Hellen
Sasamalo, Mohamed
Mhimbira, Francis
Rutaihwa, Liliana K.
Droz, Sara
Schaller, Sarah
Reither, Klaus
Hilty, Markus
Comas, Inaki
Beisel, Christian
Schmid, Christoph D.
Fenner, Lukas
Gagneux, Sebastien
author_sort Ticlla, Monica R.
collection PubMed
description Each day, approximately 27,000 people become ill with tuberculosis (TB), and 4,000 die from this disease. Pulmonary TB is the main clinical form of TB, and affects the lungs with a considerably heterogeneous manifestation among patients. Immunomodulation by an interplay of host-, environment-, and pathogen-associated factors partially explains such heterogeneity. Microbial communities residing in the host's airways have immunomodulatory effects, but it is unclear if the inter-individual variability of these microbial communities is associated with the heterogeneity of pulmonary TB. Here, we investigated this possibility by characterizing the microbial composition in the sputum of 334 TB patients from Tanzania, and by assessing its association with three aspects of disease manifestations: sputum mycobacterial load, severe clinical findings, and chest x-ray (CXR) findings. Compositional data analysis of taxonomic profiles based on 16S-rRNA gene amplicon sequencing and on whole metagenome shotgun sequencing, and graph-based inference of microbial associations revealed that the airway microbiome of TB patients was shaped by inverse relationships between Streptococcus and two anaerobes: Selenomonas and Fusobacterium. Specifically, the strength of these microbial associations was negatively correlated with Faith's phylogenetic diversity (PD) and with the accumulation of transient genera. Furthermore, low body mass index (BMI) determined the association between abnormal CXRs and community diversity and composition. These associations were mediated by increased abundance of Selenomonas and Fusobacterium, relative to the abundance of Streptococcus, in underweight patients with lung parenchymal infiltrates and in comparison to those with normal chest x-rays. And last, the detection of herpesviruses and anelloviruses in sputum microbial assemblage was linked to co-infection with HIV. Given the anaerobic metabolism of Selenomonas and Fusobacterium, and the hypoxic environment of lung infiltrates, our results suggest that in underweight TB patients, lung tissue remodeling toward anaerobic conditions favors the growth of Selenomonas and Fusobacterium at the expense of Streptococcus. These new insights into the interplay among particular members of the airway microbiome, BMI, and lung parenchymal lesions in TB patients, add a new dimension to the long-known association between low BMI and pulmonary TB. Our results also drive attention to the airways virome in the context of HIV-TB coinfection.
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spelling pubmed-84178042021-09-05 The Sputum Microbiome in Pulmonary Tuberculosis and Its Association With Disease Manifestations: A Cross-Sectional Study Ticlla, Monica R. Hella, Jerry Hiza, Hellen Sasamalo, Mohamed Mhimbira, Francis Rutaihwa, Liliana K. Droz, Sara Schaller, Sarah Reither, Klaus Hilty, Markus Comas, Inaki Beisel, Christian Schmid, Christoph D. Fenner, Lukas Gagneux, Sebastien Front Microbiol Microbiology Each day, approximately 27,000 people become ill with tuberculosis (TB), and 4,000 die from this disease. Pulmonary TB is the main clinical form of TB, and affects the lungs with a considerably heterogeneous manifestation among patients. Immunomodulation by an interplay of host-, environment-, and pathogen-associated factors partially explains such heterogeneity. Microbial communities residing in the host's airways have immunomodulatory effects, but it is unclear if the inter-individual variability of these microbial communities is associated with the heterogeneity of pulmonary TB. Here, we investigated this possibility by characterizing the microbial composition in the sputum of 334 TB patients from Tanzania, and by assessing its association with three aspects of disease manifestations: sputum mycobacterial load, severe clinical findings, and chest x-ray (CXR) findings. Compositional data analysis of taxonomic profiles based on 16S-rRNA gene amplicon sequencing and on whole metagenome shotgun sequencing, and graph-based inference of microbial associations revealed that the airway microbiome of TB patients was shaped by inverse relationships between Streptococcus and two anaerobes: Selenomonas and Fusobacterium. Specifically, the strength of these microbial associations was negatively correlated with Faith's phylogenetic diversity (PD) and with the accumulation of transient genera. Furthermore, low body mass index (BMI) determined the association between abnormal CXRs and community diversity and composition. These associations were mediated by increased abundance of Selenomonas and Fusobacterium, relative to the abundance of Streptococcus, in underweight patients with lung parenchymal infiltrates and in comparison to those with normal chest x-rays. And last, the detection of herpesviruses and anelloviruses in sputum microbial assemblage was linked to co-infection with HIV. Given the anaerobic metabolism of Selenomonas and Fusobacterium, and the hypoxic environment of lung infiltrates, our results suggest that in underweight TB patients, lung tissue remodeling toward anaerobic conditions favors the growth of Selenomonas and Fusobacterium at the expense of Streptococcus. These new insights into the interplay among particular members of the airway microbiome, BMI, and lung parenchymal lesions in TB patients, add a new dimension to the long-known association between low BMI and pulmonary TB. Our results also drive attention to the airways virome in the context of HIV-TB coinfection. Frontiers Media S.A. 2021-08-20 /pmc/articles/PMC8417804/ /pubmed/34489876 http://dx.doi.org/10.3389/fmicb.2021.633396 Text en Copyright © 2021 Ticlla, Hella, Hiza, Sasamalo, Mhimbira, Rutaihwa, Droz, Schaller, Reither, Hilty, Comas, Beisel, Schmid, Fenner and Gagneux. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Ticlla, Monica R.
Hella, Jerry
Hiza, Hellen
Sasamalo, Mohamed
Mhimbira, Francis
Rutaihwa, Liliana K.
Droz, Sara
Schaller, Sarah
Reither, Klaus
Hilty, Markus
Comas, Inaki
Beisel, Christian
Schmid, Christoph D.
Fenner, Lukas
Gagneux, Sebastien
The Sputum Microbiome in Pulmonary Tuberculosis and Its Association With Disease Manifestations: A Cross-Sectional Study
title The Sputum Microbiome in Pulmonary Tuberculosis and Its Association With Disease Manifestations: A Cross-Sectional Study
title_full The Sputum Microbiome in Pulmonary Tuberculosis and Its Association With Disease Manifestations: A Cross-Sectional Study
title_fullStr The Sputum Microbiome in Pulmonary Tuberculosis and Its Association With Disease Manifestations: A Cross-Sectional Study
title_full_unstemmed The Sputum Microbiome in Pulmonary Tuberculosis and Its Association With Disease Manifestations: A Cross-Sectional Study
title_short The Sputum Microbiome in Pulmonary Tuberculosis and Its Association With Disease Manifestations: A Cross-Sectional Study
title_sort sputum microbiome in pulmonary tuberculosis and its association with disease manifestations: a cross-sectional study
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417804/
https://www.ncbi.nlm.nih.gov/pubmed/34489876
http://dx.doi.org/10.3389/fmicb.2021.633396
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