Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort

The syndrome of spontaneous preterm birth (sPTB) presents a challenge to mechanistic understanding, effective risk stratification, and clinical management. Individual associations between sPTB, self-reported ethnic ancestry, vaginal microbiota, metabolome, and innate immune response are known but no...

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Main Authors: Flavia Flaviani, Natasha L. Hezelgrave, Tokuwa Kanno, Erica M. Prosdocimi, Evonne Chin-Smith, Alexandra E. Ridout, Djuna K. von Maydell, Vikash Mistry, William G. Wade, Andrew H. Shennan, Konstantina Dimitrakopoulou, Paul T. Seed, A. James Mason, Rachel M. Tribe
Format: Article
Language:English
Published: American Society for Clinical investigation 2021-08-01
Series:JCI Insight
Subjects:
Online Access:https://doi.org/10.1172/jci.insight.149257
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author Flavia Flaviani
Natasha L. Hezelgrave
Tokuwa Kanno
Erica M. Prosdocimi
Evonne Chin-Smith
Alexandra E. Ridout
Djuna K. von Maydell
Vikash Mistry
William G. Wade
Andrew H. Shennan
Konstantina Dimitrakopoulou
Paul T. Seed
A. James Mason
Rachel M. Tribe
author_facet Flavia Flaviani
Natasha L. Hezelgrave
Tokuwa Kanno
Erica M. Prosdocimi
Evonne Chin-Smith
Alexandra E. Ridout
Djuna K. von Maydell
Vikash Mistry
William G. Wade
Andrew H. Shennan
Konstantina Dimitrakopoulou
Paul T. Seed
A. James Mason
Rachel M. Tribe
author_sort Flavia Flaviani
collection DOAJ
description The syndrome of spontaneous preterm birth (sPTB) presents a challenge to mechanistic understanding, effective risk stratification, and clinical management. Individual associations between sPTB, self-reported ethnic ancestry, vaginal microbiota, metabolome, and innate immune response are known but not fully understood, and knowledge has yet to impact clinical practice. Here, we used multi–data type integration and composite statistical models to gain insight into sPTB risk by exploring the cervicovaginal environment of an ethnically heterogenous pregnant population (n = 346 women; n = 60 sPTB < 37 weeks’ gestation, including n = 27 sPTB < 34 weeks). Analysis of cervicovaginal samples (10–15+6 weeks) identified potentially novel interactions between risk of sPTB and microbiota, metabolite, and maternal host defense molecules. Statistical modeling identified a composite of metabolites (leucine, tyrosine, aspartate, lactate, betaine, acetate, and Ca2+) associated with risk of sPTB < 37 weeks (AUC 0.752). A combination of glucose, aspartate, Ca2+, Lactobacillus crispatus, and L. acidophilus relative abundance identified risk of early sPTB < 34 weeks (AUC 0.758), improved by stratification by ethnicity (AUC 0.835). Increased relative abundance of L. acidophilus appeared protective against sPTB < 34 weeks. By using cervicovaginal fluid samples, we demonstrate the potential of multi–data type integration for developing composite models toward understanding the contribution of the vaginal environment to risk of sPTB.
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spelling doaj.art-2cb446a32e994b038f2a02ad6794749e2022-12-22T00:31:05ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-08-01616Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohortFlavia FlavianiNatasha L. HezelgraveTokuwa KannoErica M. ProsdocimiEvonne Chin-SmithAlexandra E. RidoutDjuna K. von MaydellVikash MistryWilliam G. WadeAndrew H. ShennanKonstantina DimitrakopoulouPaul T. SeedA. James MasonRachel M. TribeThe syndrome of spontaneous preterm birth (sPTB) presents a challenge to mechanistic understanding, effective risk stratification, and clinical management. Individual associations between sPTB, self-reported ethnic ancestry, vaginal microbiota, metabolome, and innate immune response are known but not fully understood, and knowledge has yet to impact clinical practice. Here, we used multi–data type integration and composite statistical models to gain insight into sPTB risk by exploring the cervicovaginal environment of an ethnically heterogenous pregnant population (n = 346 women; n = 60 sPTB < 37 weeks’ gestation, including n = 27 sPTB < 34 weeks). Analysis of cervicovaginal samples (10–15+6 weeks) identified potentially novel interactions between risk of sPTB and microbiota, metabolite, and maternal host defense molecules. Statistical modeling identified a composite of metabolites (leucine, tyrosine, aspartate, lactate, betaine, acetate, and Ca2+) associated with risk of sPTB < 37 weeks (AUC 0.752). A combination of glucose, aspartate, Ca2+, Lactobacillus crispatus, and L. acidophilus relative abundance identified risk of early sPTB < 34 weeks (AUC 0.758), improved by stratification by ethnicity (AUC 0.835). Increased relative abundance of L. acidophilus appeared protective against sPTB < 34 weeks. By using cervicovaginal fluid samples, we demonstrate the potential of multi–data type integration for developing composite models toward understanding the contribution of the vaginal environment to risk of sPTB.https://doi.org/10.1172/jci.insight.149257MicrobiologyReproductive biology
spellingShingle Flavia Flaviani
Natasha L. Hezelgrave
Tokuwa Kanno
Erica M. Prosdocimi
Evonne Chin-Smith
Alexandra E. Ridout
Djuna K. von Maydell
Vikash Mistry
William G. Wade
Andrew H. Shennan
Konstantina Dimitrakopoulou
Paul T. Seed
A. James Mason
Rachel M. Tribe
Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort
JCI Insight
Microbiology
Reproductive biology
title Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort
title_full Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort
title_fullStr Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort
title_full_unstemmed Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort
title_short Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort
title_sort cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort
topic Microbiology
Reproductive biology
url https://doi.org/10.1172/jci.insight.149257
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