Cervicovaginal Microbiome Composition Is Associated with Metabolic Profiles in Healthy Pregnancy

ABSTRACT Microbes and their metabolic products influence early-life immune and microbiome development, yet remain understudied during pregnancy. Vaginal microbial communities are typically dominated by one or a few well-adapted microbes which are able to survive in a narrow pH range and are adapted...

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Autores principales: Andrew Oliver, Brandon LaMere, Claudia Weihe, Stephen Wandro, Karen L. Lindsay, Pathik D. Wadhwa, David A. Mills, David T. Pride, Oliver Fiehn, Trent Northen, Markus de Raad, Huiying Li, Jennifer B. H. Martiny, Susan Lynch, Katrine Whiteson
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Publicado: American Society for Microbiology 2020
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spelling oai:doaj.org-article:f4e8854bb24d4e67b8a96399ddc773602021-11-15T15:56:44ZCervicovaginal Microbiome Composition Is Associated with Metabolic Profiles in Healthy Pregnancy10.1128/mBio.01851-202150-7511https://doaj.org/article/f4e8854bb24d4e67b8a96399ddc773602020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01851-20https://doaj.org/toc/2150-7511ABSTRACT Microbes and their metabolic products influence early-life immune and microbiome development, yet remain understudied during pregnancy. Vaginal microbial communities are typically dominated by one or a few well-adapted microbes which are able to survive in a narrow pH range and are adapted to live on host-derived carbon sources, likely sourced from glycogen and mucin present in the vaginal environment. We characterized the cervicovaginal microbiomes of 16 healthy women throughout the three trimesters of pregnancy. Additionally, we analyzed saliva and urine metabolomes using gas chromatography-time of flight mass spectrometry (GC-TOF MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) lipidomics approaches for samples from mothers and their infants through the first year of life. Amplicon sequencing revealed most women had either a simple community with one highly abundant species of Lactobacillus or a more diverse community characterized by a high abundance of Gardnerella, as has also been previously described in several independent cohorts. Integrating GC-TOF MS and lipidomics data with amplicon sequencing, we found metabolites that distinctly associate with particular communities. For example, cervicovaginal microbial communities dominated by Lactobacillus crispatus have high mannitol levels, which is unexpected given the characterization of L. crispatus as a homofermentative Lactobacillus species. It may be that fluctuations in which Lactobacillus dominate a particular vaginal microbiome are dictated by the availability of host sugars, such as fructose, which is the most likely substrate being converted to mannitol. Overall, using a multi-“omic” approach, we begin to address the genetic and molecular means by which a particular vaginal microbiome becomes vulnerable to large changes in composition. IMPORTANCE Humans have a unique vaginal microbiome compared to other mammals, characterized by low diversity and often dominated by Lactobacillus spp. Dramatic shifts in vaginal microbial communities sometimes contribute to the presence of a polymicrobial overgrowth condition called bacterial vaginosis (BV). However, many healthy women lacking BV symptoms have vaginal microbiomes dominated by microbes associated with BV, resulting in debate about the definition of a healthy vaginal microbiome. Despite substantial evidence that the reproductive health of a woman depends on the vaginal microbiota, future therapies that may improve reproductive health outcomes are stalled due to limited understanding surrounding the ecology of the vaginal microbiome. Here, we use sequencing and metabolomic techniques to show novel associations between vaginal microbes and metabolites during healthy pregnancy. We speculate these associations underlie microbiome dynamics and may contribute to a better understanding of transitions between alternative vaginal microbiome compositions.Andrew OliverBrandon LaMereClaudia WeiheStephen WandroKaren L. LindsayPathik D. WadhwaDavid A. MillsDavid T. PrideOliver FiehnTrent NorthenMarkus de RaadHuiying LiJennifer B. H. MartinySusan LynchKatrine WhitesonAmerican Society for MicrobiologyarticleLactobacilluslongitudinalmetabolomemicrobiomepregnancyvaginaMicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020)
institution DOAJ
collection DOAJ
language EN
topic Lactobacillus
longitudinal
metabolome
microbiome
pregnancy
vagina
Microbiology
QR1-502
spellingShingle Lactobacillus
longitudinal
metabolome
microbiome
pregnancy
vagina
Microbiology
QR1-502
Andrew Oliver
Brandon LaMere
Claudia Weihe
Stephen Wandro
Karen L. Lindsay
Pathik D. Wadhwa
David A. Mills
David T. Pride
Oliver Fiehn
Trent Northen
Markus de Raad
Huiying Li
Jennifer B. H. Martiny
Susan Lynch
Katrine Whiteson
Cervicovaginal Microbiome Composition Is Associated with Metabolic Profiles in Healthy Pregnancy
description ABSTRACT Microbes and their metabolic products influence early-life immune and microbiome development, yet remain understudied during pregnancy. Vaginal microbial communities are typically dominated by one or a few well-adapted microbes which are able to survive in a narrow pH range and are adapted to live on host-derived carbon sources, likely sourced from glycogen and mucin present in the vaginal environment. We characterized the cervicovaginal microbiomes of 16 healthy women throughout the three trimesters of pregnancy. Additionally, we analyzed saliva and urine metabolomes using gas chromatography-time of flight mass spectrometry (GC-TOF MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) lipidomics approaches for samples from mothers and their infants through the first year of life. Amplicon sequencing revealed most women had either a simple community with one highly abundant species of Lactobacillus or a more diverse community characterized by a high abundance of Gardnerella, as has also been previously described in several independent cohorts. Integrating GC-TOF MS and lipidomics data with amplicon sequencing, we found metabolites that distinctly associate with particular communities. For example, cervicovaginal microbial communities dominated by Lactobacillus crispatus have high mannitol levels, which is unexpected given the characterization of L. crispatus as a homofermentative Lactobacillus species. It may be that fluctuations in which Lactobacillus dominate a particular vaginal microbiome are dictated by the availability of host sugars, such as fructose, which is the most likely substrate being converted to mannitol. Overall, using a multi-“omic” approach, we begin to address the genetic and molecular means by which a particular vaginal microbiome becomes vulnerable to large changes in composition. IMPORTANCE Humans have a unique vaginal microbiome compared to other mammals, characterized by low diversity and often dominated by Lactobacillus spp. Dramatic shifts in vaginal microbial communities sometimes contribute to the presence of a polymicrobial overgrowth condition called bacterial vaginosis (BV). However, many healthy women lacking BV symptoms have vaginal microbiomes dominated by microbes associated with BV, resulting in debate about the definition of a healthy vaginal microbiome. Despite substantial evidence that the reproductive health of a woman depends on the vaginal microbiota, future therapies that may improve reproductive health outcomes are stalled due to limited understanding surrounding the ecology of the vaginal microbiome. Here, we use sequencing and metabolomic techniques to show novel associations between vaginal microbes and metabolites during healthy pregnancy. We speculate these associations underlie microbiome dynamics and may contribute to a better understanding of transitions between alternative vaginal microbiome compositions.
format article
author Andrew Oliver
Brandon LaMere
Claudia Weihe
Stephen Wandro
Karen L. Lindsay
Pathik D. Wadhwa
David A. Mills
David T. Pride
Oliver Fiehn
Trent Northen
Markus de Raad
Huiying Li
Jennifer B. H. Martiny
Susan Lynch
Katrine Whiteson
author_facet Andrew Oliver
Brandon LaMere
Claudia Weihe
Stephen Wandro
Karen L. Lindsay
Pathik D. Wadhwa
David A. Mills
David T. Pride
Oliver Fiehn
Trent Northen
Markus de Raad
Huiying Li
Jennifer B. H. Martiny
Susan Lynch
Katrine Whiteson
author_sort Andrew Oliver
title Cervicovaginal Microbiome Composition Is Associated with Metabolic Profiles in Healthy Pregnancy
title_short Cervicovaginal Microbiome Composition Is Associated with Metabolic Profiles in Healthy Pregnancy
title_full Cervicovaginal Microbiome Composition Is Associated with Metabolic Profiles in Healthy Pregnancy
title_fullStr Cervicovaginal Microbiome Composition Is Associated with Metabolic Profiles in Healthy Pregnancy
title_full_unstemmed Cervicovaginal Microbiome Composition Is Associated with Metabolic Profiles in Healthy Pregnancy
title_sort cervicovaginal microbiome composition is associated with metabolic profiles in healthy pregnancy
publisher American Society for Microbiology
publishDate 2020
url https://doaj.org/article/f4e8854bb24d4e67b8a96399ddc77360
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