Correlation between Disease Severity and the Intestinal Microbiome in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>-Infected Rhesus Macaques

ABSTRACT The factors that determine host susceptibility to tuberculosis (TB) are poorly defined. The microbiota has been identified as a key influence on the nutritional, metabolic, and immunological status of the host, although its role in the pathogenesis of TB is currently unclear. Here, we inves...

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Autores principales:	Sivaranjani Namasivayam, Keith D. Kauffman, John A. McCulloch, Wuxing Yuan, Vishal Thovarai, Lara R. Mittereder, Giorgio Trinchieri, Daniel L. Barber, Alan Sher
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	microbiome nonhuman primate tuberculosis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f79ef64a4ff94b528aef9897757a8ce5
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spelling	oai:doaj.org-article:f79ef64a4ff94b528aef9897757a8ce52021-11-15T15:55:25ZCorrelation between Disease Severity and the Intestinal Microbiome in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>-Infected Rhesus Macaques10.1128/mBio.01018-192150-7511https://doaj.org/article/f79ef64a4ff94b528aef9897757a8ce52019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01018-19https://doaj.org/toc/2150-7511ABSTRACT The factors that determine host susceptibility to tuberculosis (TB) are poorly defined. The microbiota has been identified as a key influence on the nutritional, metabolic, and immunological status of the host, although its role in the pathogenesis of TB is currently unclear. Here, we investigated the influence of Mycobacterium tuberculosis exposure on the microbiome and conversely the impact of the intestinal microbiome on the outcome of M. tuberculosis exposure in a rhesus macaque model of tuberculosis. Animals were infected with different strains and doses of M. tuberculosis in three independent experiments, resulting in a range of disease severities. The compositions of the microbiotas were then assessed using a combination of 16S rRNA and metagenomic sequencing in fecal samples collected pre- and postinfection. Clustering analyses of the microbiota compositions revealed that alterations in the microbiome after M. tuberculosis infection were of much lower magnitude than the variability seen between individual monkeys. However, the microbiomes of macaques that developed severe disease were noticeably distinct from those of the animals with less severe disease as well as from each other. In particular, the bacterial families Lachnospiraceae and Clostridiaceae were enriched in monkeys that were more susceptible to infection, while numbers of Streptococcaceae were decreased. These findings in infected nonhuman primates reveal that certain baseline microbiome communities may strongly associate with the development of severe tuberculosis following infection and can be more important disease correlates than alterations to the microbiota following M. tuberculosis infection itself. IMPORTANCE Why some but not all individuals infected with Mycobacterium tuberculosis develop disease is poorly understood. Previous studies have revealed an important influence of the microbiota on host resistance to infection with a number of different disease agents. Here, we investigated the possible role of the individual’s microbiome in impacting the outcome of M. tuberculosis infection in rhesus monkeys experimentally exposed to this important human pathogen. Although M. tuberculosis infection itself caused only minor alterations in the composition of the gut microbiota in these animals, we observed a significant correlation between an individual monkey’s microbiome and the severity of pulmonary disease. More importantly, this correlation between microbiota structure and disease outcome was evident even prior to infection. Taken together, our findings suggest that the composition of the microbiome may be a useful predictor of tuberculosis progression in infected individuals either directly because of the microbiome’s direct influence on host resistance or indirectly because of its association with other host factors that have this influence. This calls for exploration of the potential of the microbiota composition as a predictive biomarker through carefully designed prospective studies.Sivaranjani NamasivayamKeith D. KauffmanJohn A. McCullochWuxing YuanVishal ThovaraiLara R. MitterederGiorgio TrinchieriDaniel L. BarberAlan SherAmerican Society for Microbiologyarticlemicrobiomenonhuman primatetuberculosisMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	microbiome nonhuman primate tuberculosis Microbiology QR1-502
spellingShingle	microbiome nonhuman primate tuberculosis Microbiology QR1-502 Sivaranjani Namasivayam Keith D. Kauffman John A. McCulloch Wuxing Yuan Vishal Thovarai Lara R. Mittereder Giorgio Trinchieri Daniel L. Barber Alan Sher Correlation between Disease Severity and the Intestinal Microbiome in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>-Infected Rhesus Macaques
description	ABSTRACT The factors that determine host susceptibility to tuberculosis (TB) are poorly defined. The microbiota has been identified as a key influence on the nutritional, metabolic, and immunological status of the host, although its role in the pathogenesis of TB is currently unclear. Here, we investigated the influence of Mycobacterium tuberculosis exposure on the microbiome and conversely the impact of the intestinal microbiome on the outcome of M. tuberculosis exposure in a rhesus macaque model of tuberculosis. Animals were infected with different strains and doses of M. tuberculosis in three independent experiments, resulting in a range of disease severities. The compositions of the microbiotas were then assessed using a combination of 16S rRNA and metagenomic sequencing in fecal samples collected pre- and postinfection. Clustering analyses of the microbiota compositions revealed that alterations in the microbiome after M. tuberculosis infection were of much lower magnitude than the variability seen between individual monkeys. However, the microbiomes of macaques that developed severe disease were noticeably distinct from those of the animals with less severe disease as well as from each other. In particular, the bacterial families Lachnospiraceae and Clostridiaceae were enriched in monkeys that were more susceptible to infection, while numbers of Streptococcaceae were decreased. These findings in infected nonhuman primates reveal that certain baseline microbiome communities may strongly associate with the development of severe tuberculosis following infection and can be more important disease correlates than alterations to the microbiota following M. tuberculosis infection itself. IMPORTANCE Why some but not all individuals infected with Mycobacterium tuberculosis develop disease is poorly understood. Previous studies have revealed an important influence of the microbiota on host resistance to infection with a number of different disease agents. Here, we investigated the possible role of the individual’s microbiome in impacting the outcome of M. tuberculosis infection in rhesus monkeys experimentally exposed to this important human pathogen. Although M. tuberculosis infection itself caused only minor alterations in the composition of the gut microbiota in these animals, we observed a significant correlation between an individual monkey’s microbiome and the severity of pulmonary disease. More importantly, this correlation between microbiota structure and disease outcome was evident even prior to infection. Taken together, our findings suggest that the composition of the microbiome may be a useful predictor of tuberculosis progression in infected individuals either directly because of the microbiome’s direct influence on host resistance or indirectly because of its association with other host factors that have this influence. This calls for exploration of the potential of the microbiota composition as a predictive biomarker through carefully designed prospective studies.
format	article
author	Sivaranjani Namasivayam Keith D. Kauffman John A. McCulloch Wuxing Yuan Vishal Thovarai Lara R. Mittereder Giorgio Trinchieri Daniel L. Barber Alan Sher
author_facet	Sivaranjani Namasivayam Keith D. Kauffman John A. McCulloch Wuxing Yuan Vishal Thovarai Lara R. Mittereder Giorgio Trinchieri Daniel L. Barber Alan Sher
author_sort	Sivaranjani Namasivayam
title	Correlation between Disease Severity and the Intestinal Microbiome in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>-Infected Rhesus Macaques
title_short	Correlation between Disease Severity and the Intestinal Microbiome in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>-Infected Rhesus Macaques
title_full	Correlation between Disease Severity and the Intestinal Microbiome in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>-Infected Rhesus Macaques
title_fullStr	Correlation between Disease Severity and the Intestinal Microbiome in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>-Infected Rhesus Macaques
title_full_unstemmed	Correlation between Disease Severity and the Intestinal Microbiome in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>-Infected Rhesus Macaques
title_sort	correlation between disease severity and the intestinal microbiome in <named-content content-type="genus-species">mycobacterium tuberculosis</named-content>-infected rhesus macaques
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/f79ef64a4ff94b528aef9897757a8ce5
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Correlation between Disease Severity and the Intestinal Microbiome in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>-Infected Rhesus Macaques

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