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Profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure
BACKGROUND: The specific interactions of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), and the lung microbiota in infection are entirely unexplored. Studies in cancer and other infectious diseases suggest that there are important exchanges occurring between host and mic...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178261/ https://www.ncbi.nlm.nih.gov/pubmed/30301469 http://dx.doi.org/10.1186/s40168-018-0560-y |
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author | Cadena, Anthony M Ma, Yixuan Ding, Tao Bryant, MacKenzie Maiello, Pauline Geber, Adam Lin, Philana Ling Flynn, JoAnne L Ghedin, Elodie |
author_facet | Cadena, Anthony M Ma, Yixuan Ding, Tao Bryant, MacKenzie Maiello, Pauline Geber, Adam Lin, Philana Ling Flynn, JoAnne L Ghedin, Elodie |
author_sort | Cadena, Anthony M |
collection | PubMed |
description | BACKGROUND: The specific interactions of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), and the lung microbiota in infection are entirely unexplored. Studies in cancer and other infectious diseases suggest that there are important exchanges occurring between host and microbiota that influence the immunological landscape. This can result in alterations in immune regulation and inflammation both locally and systemically. To assess whether Mtb infection modifies the lung microbiome, and identify changes in microbial abundance and diversity as a function of pulmonary inflammation, we compared infected and uninfected lung lobe washes collected serially from 26 macaques by bronchoalveolar lavage over the course of infection. RESULTS: We found that Mtb induced an initial increase in lung microbial diversity at 1 month post infection that normalized by 5 months of infection across all macaques. Several core genera showed global shifts from baseline and throughout infection. Moreover, we identified several specific taxa normally associated with the oral microbiome that increased in relative abundance in the lung following Mtb infection, including SR1, Aggregatibacter, Leptotrichia, Prevotella, and Campylobacter. On an individual macaque level, we found significant heterogeneity in both the magnitude and duration of change within the lung microbial community that was unrelated to lung inflammation and lobe involvement as seen by positron emission tomography/computed tomography (PET/CT) imaging. By comparing microbial interaction networks pre- and post-infection using the predictive algorithm SPIEC-EASI, we observe that extra connections are gained by Actinomycetales, the order containing Mtb, in spite of an overall reduction in the number of interactions of the whole community post-infection, implicating Mtb-driven ecological reorganization within the lung. CONCLUSIONS: This study is the first to probe the dynamic interplay between Mtb and host microbiota longitudinally and in the macaque lung. Our findings suggest that Mtb can alter the microbial landscape of infected lung lobes and that these interactions induce dysbiosis that can disrupt oral-airway boundaries, shift overall lung diversity, and modulate specific microbial relationships. We also provide evidence that this effect is heterogeneous across different macaques. Overall, however, the changes to the airway microbiota after Mtb infection were surprisingly modest, despite a range of Mtb-induced pulmonary inflammation in this cohort of macaques. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-018-0560-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6178261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-61782612018-10-18 Profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure Cadena, Anthony M Ma, Yixuan Ding, Tao Bryant, MacKenzie Maiello, Pauline Geber, Adam Lin, Philana Ling Flynn, JoAnne L Ghedin, Elodie Microbiome Research BACKGROUND: The specific interactions of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), and the lung microbiota in infection are entirely unexplored. Studies in cancer and other infectious diseases suggest that there are important exchanges occurring between host and microbiota that influence the immunological landscape. This can result in alterations in immune regulation and inflammation both locally and systemically. To assess whether Mtb infection modifies the lung microbiome, and identify changes in microbial abundance and diversity as a function of pulmonary inflammation, we compared infected and uninfected lung lobe washes collected serially from 26 macaques by bronchoalveolar lavage over the course of infection. RESULTS: We found that Mtb induced an initial increase in lung microbial diversity at 1 month post infection that normalized by 5 months of infection across all macaques. Several core genera showed global shifts from baseline and throughout infection. Moreover, we identified several specific taxa normally associated with the oral microbiome that increased in relative abundance in the lung following Mtb infection, including SR1, Aggregatibacter, Leptotrichia, Prevotella, and Campylobacter. On an individual macaque level, we found significant heterogeneity in both the magnitude and duration of change within the lung microbial community that was unrelated to lung inflammation and lobe involvement as seen by positron emission tomography/computed tomography (PET/CT) imaging. By comparing microbial interaction networks pre- and post-infection using the predictive algorithm SPIEC-EASI, we observe that extra connections are gained by Actinomycetales, the order containing Mtb, in spite of an overall reduction in the number of interactions of the whole community post-infection, implicating Mtb-driven ecological reorganization within the lung. CONCLUSIONS: This study is the first to probe the dynamic interplay between Mtb and host microbiota longitudinally and in the macaque lung. Our findings suggest that Mtb can alter the microbial landscape of infected lung lobes and that these interactions induce dysbiosis that can disrupt oral-airway boundaries, shift overall lung diversity, and modulate specific microbial relationships. We also provide evidence that this effect is heterogeneous across different macaques. Overall, however, the changes to the airway microbiota after Mtb infection were surprisingly modest, despite a range of Mtb-induced pulmonary inflammation in this cohort of macaques. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-018-0560-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-09 /pmc/articles/PMC6178261/ /pubmed/30301469 http://dx.doi.org/10.1186/s40168-018-0560-y Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Cadena, Anthony M Ma, Yixuan Ding, Tao Bryant, MacKenzie Maiello, Pauline Geber, Adam Lin, Philana Ling Flynn, JoAnne L Ghedin, Elodie Profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure |
title | Profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure |
title_full | Profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure |
title_fullStr | Profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure |
title_full_unstemmed | Profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure |
title_short | Profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure |
title_sort | profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178261/ https://www.ncbi.nlm.nih.gov/pubmed/30301469 http://dx.doi.org/10.1186/s40168-018-0560-y |
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