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...
Main Authors: | , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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American Society for Clinical investigation
2021-08-01
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Series: | JCI Insight |
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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. |
first_indexed | 2024-12-12T08:31:16Z |
format | Article |
id | doaj.art-2cb446a32e994b038f2a02ad6794749e |
institution | Directory Open Access Journal |
issn | 2379-3708 |
language | English |
last_indexed | 2024-12-12T08:31:16Z |
publishDate | 2021-08-01 |
publisher | American Society for Clinical investigation |
record_format | Article |
series | JCI Insight |
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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