Compositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhi

ABSTRACT Insights into disease susceptibility as well as the efficacy of vaccines against typhoid and other enteric pathogens may be informed by better understanding the relationship between the effector immune response and the gut microbiota. In the present study, we characterized the composition (...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yan Zhang, Arthur Brady, Cheron Jones, Yang Song, Thomas C. Darton, Claire Jones, Christoph J. Blohmke, Andrew J. Pollard, Laurence S. Magder, Alessio Fasano, Marcelo B. Sztein, Claire M. Fraser
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	16S rRNA gene profiling Salmonella immunization metatranscriptomics methanogens microbiome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/544db5e9874840318d38f19327f53171
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:544db5e9874840318d38f19327f53171
record_format	dspace
spelling	oai:doaj.org-article:544db5e9874840318d38f19327f531712021-11-15T16:00:26ZCompositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhi10.1128/mBio.00686-182150-7511https://doaj.org/article/544db5e9874840318d38f19327f531712018-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00686-18https://doaj.org/toc/2150-7511ABSTRACT Insights into disease susceptibility as well as the efficacy of vaccines against typhoid and other enteric pathogens may be informed by better understanding the relationship between the effector immune response and the gut microbiota. In the present study, we characterized the composition (16S rRNA gene profiling) and function (RNA sequencing [RNA-seq]) of the gut microbiota following immunization and subsequent exposure to wild-type Salmonella enterica serovar Typhi in a human challenge model to further investigate the central hypothesis that clinical outcomes may be linked to the gut microbiota. Metatranscriptome analysis of longitudinal stool samples collected from study subjects revealed two stable patterns of gene expression for the human gut microbiota, dominated by transcripts from either Methanobrevibacter or a diverse representation of genera in the Firmicutes phylum. Immunization with one of two live oral attenuated vaccines against S. Typhi had minimal effects on the composition or function of the gut microbiota. It was observed that subjects harboring the methanogen-dominated transcriptome community at baseline displayed a lower risk of developing symptoms of typhoid following challenge with wild-type S. Typhi. Furthermore, genes encoding antioxidant proteins, metal homeostasis and transport proteins, and heat shock proteins were expressed at a higher level at baseline or after challenge with S. Typhi in subjects who did not develop symptoms of typhoid. These data suggest that functional differences relating to redox potential and ion homeostasis in the gut microbiota may impact clinical outcomes following exposure to wild-type S. Typhi. IMPORTANCE S. Typhi is a significant cause of systemic febrile morbidity in settings with poor sanitation and limited access to clean water. It has been demonstrated that the human gut microbiota can influence mucosal immune responses, but there is little information available on the impact of the human gut microbiota on clinical outcomes following exposure to enteric pathogens. Here, we describe differences in the composition and function of the gut microbiota in healthy adult volunteers enrolled in a typhoid vaccine trial and report that these differences are associated with host susceptibility to or protection from typhoid after challenge with wild-type S. Typhi. Our observations have important implications in interpreting the efficacy of oral attenuated vaccines against enteric pathogens in diverse populations.Yan ZhangArthur BradyCheron JonesYang SongThomas C. DartonClaire JonesChristoph J. BlohmkeAndrew J. PollardLaurence S. MagderAlessio FasanoMarcelo B. SzteinClaire M. FraserAmerican Society for Microbiologyarticle16S rRNA gene profilingSalmonellaimmunizationmetatranscriptomicsmethanogensmicrobiomeMicrobiologyQR1-502ENmBio, Vol 9, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	16S rRNA gene profiling Salmonella immunization metatranscriptomics methanogens microbiome Microbiology QR1-502
spellingShingle	16S rRNA gene profiling Salmonella immunization metatranscriptomics methanogens microbiome Microbiology QR1-502 Yan Zhang Arthur Brady Cheron Jones Yang Song Thomas C. Darton Claire Jones Christoph J. Blohmke Andrew J. Pollard Laurence S. Magder Alessio Fasano Marcelo B. Sztein Claire M. Fraser Compositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhi
description	ABSTRACT Insights into disease susceptibility as well as the efficacy of vaccines against typhoid and other enteric pathogens may be informed by better understanding the relationship between the effector immune response and the gut microbiota. In the present study, we characterized the composition (16S rRNA gene profiling) and function (RNA sequencing [RNA-seq]) of the gut microbiota following immunization and subsequent exposure to wild-type Salmonella enterica serovar Typhi in a human challenge model to further investigate the central hypothesis that clinical outcomes may be linked to the gut microbiota. Metatranscriptome analysis of longitudinal stool samples collected from study subjects revealed two stable patterns of gene expression for the human gut microbiota, dominated by transcripts from either Methanobrevibacter or a diverse representation of genera in the Firmicutes phylum. Immunization with one of two live oral attenuated vaccines against S. Typhi had minimal effects on the composition or function of the gut microbiota. It was observed that subjects harboring the methanogen-dominated transcriptome community at baseline displayed a lower risk of developing symptoms of typhoid following challenge with wild-type S. Typhi. Furthermore, genes encoding antioxidant proteins, metal homeostasis and transport proteins, and heat shock proteins were expressed at a higher level at baseline or after challenge with S. Typhi in subjects who did not develop symptoms of typhoid. These data suggest that functional differences relating to redox potential and ion homeostasis in the gut microbiota may impact clinical outcomes following exposure to wild-type S. Typhi. IMPORTANCE S. Typhi is a significant cause of systemic febrile morbidity in settings with poor sanitation and limited access to clean water. It has been demonstrated that the human gut microbiota can influence mucosal immune responses, but there is little information available on the impact of the human gut microbiota on clinical outcomes following exposure to enteric pathogens. Here, we describe differences in the composition and function of the gut microbiota in healthy adult volunteers enrolled in a typhoid vaccine trial and report that these differences are associated with host susceptibility to or protection from typhoid after challenge with wild-type S. Typhi. Our observations have important implications in interpreting the efficacy of oral attenuated vaccines against enteric pathogens in diverse populations.
format	article
author	Yan Zhang Arthur Brady Cheron Jones Yang Song Thomas C. Darton Claire Jones Christoph J. Blohmke Andrew J. Pollard Laurence S. Magder Alessio Fasano Marcelo B. Sztein Claire M. Fraser
author_facet	Yan Zhang Arthur Brady Cheron Jones Yang Song Thomas C. Darton Claire Jones Christoph J. Blohmke Andrew J. Pollard Laurence S. Magder Alessio Fasano Marcelo B. Sztein Claire M. Fraser
author_sort	Yan Zhang
title	Compositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhi
title_short	Compositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhi
title_full	Compositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhi
title_fullStr	Compositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhi
title_full_unstemmed	Compositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhi
title_sort	compositional and functional differences in the human gut microbiome correlate with clinical outcome following infection with wild-type <named-content content-type="genus-species">salmonella enterica</named-content> serovar typhi
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/544db5e9874840318d38f19327f53171
work_keys_str_mv	AT yanzhang compositionalandfunctionaldifferencesinthehumangutmicrobiomecorrelatewithclinicaloutcomefollowinginfectionwithwildtypenamedcontentcontenttypegenusspeciessalmonellaentericanamedcontentserovartyphi AT arthurbrady compositionalandfunctionaldifferencesinthehumangutmicrobiomecorrelatewithclinicaloutcomefollowinginfectionwithwildtypenamedcontentcontenttypegenusspeciessalmonellaentericanamedcontentserovartyphi AT cheronjones compositionalandfunctionaldifferencesinthehumangutmicrobiomecorrelatewithclinicaloutcomefollowinginfectionwithwildtypenamedcontentcontenttypegenusspeciessalmonellaentericanamedcontentserovartyphi AT yangsong compositionalandfunctionaldifferencesinthehumangutmicrobiomecorrelatewithclinicaloutcomefollowinginfectionwithwildtypenamedcontentcontenttypegenusspeciessalmonellaentericanamedcontentserovartyphi AT thomascdarton compositionalandfunctionaldifferencesinthehumangutmicrobiomecorrelatewithclinicaloutcomefollowinginfectionwithwildtypenamedcontentcontenttypegenusspeciessalmonellaentericanamedcontentserovartyphi AT clairejones compositionalandfunctionaldifferencesinthehumangutmicrobiomecorrelatewithclinicaloutcomefollowinginfectionwithwildtypenamedcontentcontenttypegenusspeciessalmonellaentericanamedcontentserovartyphi AT christophjblohmke compositionalandfunctionaldifferencesinthehumangutmicrobiomecorrelatewithclinicaloutcomefollowinginfectionwithwildtypenamedcontentcontenttypegenusspeciessalmonellaentericanamedcontentserovartyphi AT andrewjpollard compositionalandfunctionaldifferencesinthehumangutmicrobiomecorrelatewithclinicaloutcomefollowinginfectionwithwildtypenamedcontentcontenttypegenusspeciessalmonellaentericanamedcontentserovartyphi AT laurencesmagder compositionalandfunctionaldifferencesinthehumangutmicrobiomecorrelatewithclinicaloutcomefollowinginfectionwithwildtypenamedcontentcontenttypegenusspeciessalmonellaentericanamedcontentserovartyphi AT alessiofasano compositionalandfunctionaldifferencesinthehumangutmicrobiomecorrelatewithclinicaloutcomefollowinginfectionwithwildtypenamedcontentcontenttypegenusspeciessalmonellaentericanamedcontentserovartyphi AT marcelobsztein compositionalandfunctionaldifferencesinthehumangutmicrobiomecorrelatewithclinicaloutcomefollowinginfectionwithwildtypenamedcontentcontenttypegenusspeciessalmonellaentericanamedcontentserovartyphi AT clairemfraser compositionalandfunctionaldifferencesinthehumangutmicrobiomecorrelatewithclinicaloutcomefollowinginfectionwithwildtypenamedcontentcontenttypegenusspeciessalmonellaentericanamedcontentserovartyphi
_version_	1718426966319693824

Compositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhi

Ejemplares similares