Profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure
Abstract 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...
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doaj-77609f03c99a4bda83e8b89614a5db2c2020-11-25T02:19:02ZengBMCMicrobiome2049-26182018-10-016111210.1186/s40168-018-0560-yProfiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structureAnthony M Cadena0Yixuan Ma1Tao Ding2MacKenzie Bryant3Pauline Maiello4Adam Geber5Philana Ling Lin6JoAnne L Flynn7Elodie Ghedin8Department of Microbiology and Molecular Genetics, University of Pittsburgh School of MedicineCenter for Genomics and Systems Biology, Department of Biology, New York UniversityCenter for Genomics and Systems Biology, Department of Biology, New York UniversityDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of MedicineDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of MedicineCenter for Genomics and Systems Biology, Department of Biology, New York UniversityDepartment of Pediatrics, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, University of Pittsburgh School of MedicineDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of MedicineCenter for Genomics and Systems Biology, Department of Biology, New York UniversityAbstract 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.http://link.springer.com/article/10.1186/s40168-018-0560-yMycobacterium tuberculosisLung and airway microbiotaMicrobiome16S rRNA geneCynomolgus macaque |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anthony M Cadena Yixuan Ma Tao Ding MacKenzie Bryant Pauline Maiello Adam Geber Philana Ling Lin JoAnne L Flynn Elodie Ghedin |
spellingShingle |
Anthony M Cadena Yixuan Ma Tao Ding MacKenzie Bryant Pauline Maiello Adam Geber Philana Ling Lin JoAnne L Flynn Elodie Ghedin Profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure Microbiome Mycobacterium tuberculosis Lung and airway microbiota Microbiome 16S rRNA gene Cynomolgus macaque |
author_facet |
Anthony M Cadena Yixuan Ma Tao Ding MacKenzie Bryant Pauline Maiello Adam Geber Philana Ling Lin JoAnne L Flynn Elodie Ghedin |
author_sort |
Anthony M Cadena |
title |
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_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_sort |
profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure |
publisher |
BMC |
series |
Microbiome |
issn |
2049-2618 |
publishDate |
2018-10-01 |
description |
Abstract 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. |
topic |
Mycobacterium tuberculosis Lung and airway microbiota Microbiome 16S rRNA gene Cynomolgus macaque |
url |
http://link.springer.com/article/10.1186/s40168-018-0560-y |
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