Human Milk Oligosaccharides Modulate the Risk for Preterm Birth in a Microbiome-Dependent and -Independent Manner

ABSTRACT Preterm birth (PTB) is one of the leading causes of neonatal mortality. The causes for spontaneous PTB are multifactorial and often remain unknown. In this study, we tested the hypothesis that human milk oligosaccharides (HMOs) in blood and urine modulate the maternal urinary and vaginal mi...

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Autores principales:	Manuela-Raluca Pausan, Vassiliki Kolovetsiou-Kreiner, Gesa Lucia Richter, Tobias Madl, Elisabeth Giselbrecht, Barbara Obermayer-Pietsch, Eva-Christine Weiss, Evelyn Jantscher-Krenn, Christine Moissl-Eichinger
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	pregnancy preterm delivery vaginal and urinary microbiome human milk oligosaccharides inflammation secretor status Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ce1160942cce4df1847ce02c6c86ac50
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spelling	oai:doaj.org-article:ce1160942cce4df1847ce02c6c86ac502021-12-02T18:23:16ZHuman Milk Oligosaccharides Modulate the Risk for Preterm Birth in a Microbiome-Dependent and -Independent Manner10.1128/mSystems.00334-202379-5077https://doaj.org/article/ce1160942cce4df1847ce02c6c86ac502020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00334-20https://doaj.org/toc/2379-5077ABSTRACT Preterm birth (PTB) is one of the leading causes of neonatal mortality. The causes for spontaneous PTB are multifactorial and often remain unknown. In this study, we tested the hypothesis that human milk oligosaccharides (HMOs) in blood and urine modulate the maternal urinary and vaginal microbiome and influence the risk for PTB. We analyzed the vaginal and urinary microbiome of a cross-sectional cohort of women with or without preterm labor and correlated our findings with measurements of metabolites and HMOs in urine and blood. We identified several microbial signatures, such as Lactobacillus jensenii, L. gasseri, Ureaplasma sp., and Gardnerella sp., associated with a short cervix, PTB, and/or preterm contractions. In addition, we observed associations between sialylated HMOs, in particular 3′-sialyllactose, with PTB, short cervix, and increased inflammation and confirmed an influence of HMOs on the microbiome profile. Since they identify serum and urinary HMOs and several key microorganisms associated with PTB, our findings point at two distinct processes modulating the risk for PTB. One process seems to be driven by sterile inflammation, characterized by increased concentrations of sialylated HMOs in serum. Another process might be microbiome mediated and potentially associated with specific HMO signatures in urine. Our results support current efforts to improve diagnostics and therapeutic strategies in PTB. IMPORTANCE The causes for preterm birth (PTB) often remain elusive. We investigated whether circulating human milk oligosaccharides (HMOs) might be involved in modulating urinary and vaginal microbiome promoting or preventing PTB. We identified here HMOs and key microbial taxa associated with indicators of PTB. Based on our results, we propose two models for how HMOs might modulate risk for PTB: (i) by changes in HMOs associated with sterile inflammation (microbiome-independent) and (ii) by HMO-driven shifts in microbiome (microbiome-dependent). Our findings will guide current efforts to better predict the risk for PTB in seemingly healthy pregnant women and also provide appropriate preventive strategies.Manuela-Raluca PausanVassiliki Kolovetsiou-KreinerGesa Lucia RichterTobias MadlElisabeth GiselbrechtBarbara Obermayer-PietschEva-Christine WeissEvelyn Jantscher-KrennChristine Moissl-EichingerAmerican Society for Microbiologyarticlepregnancypreterm deliveryvaginal and urinary microbiomehuman milk oligosaccharidesinflammationsecretor statusMicrobiologyQR1-502ENmSystems, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	pregnancy preterm delivery vaginal and urinary microbiome human milk oligosaccharides inflammation secretor status Microbiology QR1-502
spellingShingle	pregnancy preterm delivery vaginal and urinary microbiome human milk oligosaccharides inflammation secretor status Microbiology QR1-502 Manuela-Raluca Pausan Vassiliki Kolovetsiou-Kreiner Gesa Lucia Richter Tobias Madl Elisabeth Giselbrecht Barbara Obermayer-Pietsch Eva-Christine Weiss Evelyn Jantscher-Krenn Christine Moissl-Eichinger Human Milk Oligosaccharides Modulate the Risk for Preterm Birth in a Microbiome-Dependent and -Independent Manner
description	ABSTRACT Preterm birth (PTB) is one of the leading causes of neonatal mortality. The causes for spontaneous PTB are multifactorial and often remain unknown. In this study, we tested the hypothesis that human milk oligosaccharides (HMOs) in blood and urine modulate the maternal urinary and vaginal microbiome and influence the risk for PTB. We analyzed the vaginal and urinary microbiome of a cross-sectional cohort of women with or without preterm labor and correlated our findings with measurements of metabolites and HMOs in urine and blood. We identified several microbial signatures, such as Lactobacillus jensenii, L. gasseri, Ureaplasma sp., and Gardnerella sp., associated with a short cervix, PTB, and/or preterm contractions. In addition, we observed associations between sialylated HMOs, in particular 3′-sialyllactose, with PTB, short cervix, and increased inflammation and confirmed an influence of HMOs on the microbiome profile. Since they identify serum and urinary HMOs and several key microorganisms associated with PTB, our findings point at two distinct processes modulating the risk for PTB. One process seems to be driven by sterile inflammation, characterized by increased concentrations of sialylated HMOs in serum. Another process might be microbiome mediated and potentially associated with specific HMO signatures in urine. Our results support current efforts to improve diagnostics and therapeutic strategies in PTB. IMPORTANCE The causes for preterm birth (PTB) often remain elusive. We investigated whether circulating human milk oligosaccharides (HMOs) might be involved in modulating urinary and vaginal microbiome promoting or preventing PTB. We identified here HMOs and key microbial taxa associated with indicators of PTB. Based on our results, we propose two models for how HMOs might modulate risk for PTB: (i) by changes in HMOs associated with sterile inflammation (microbiome-independent) and (ii) by HMO-driven shifts in microbiome (microbiome-dependent). Our findings will guide current efforts to better predict the risk for PTB in seemingly healthy pregnant women and also provide appropriate preventive strategies.
format	article
author	Manuela-Raluca Pausan Vassiliki Kolovetsiou-Kreiner Gesa Lucia Richter Tobias Madl Elisabeth Giselbrecht Barbara Obermayer-Pietsch Eva-Christine Weiss Evelyn Jantscher-Krenn Christine Moissl-Eichinger
author_facet	Manuela-Raluca Pausan Vassiliki Kolovetsiou-Kreiner Gesa Lucia Richter Tobias Madl Elisabeth Giselbrecht Barbara Obermayer-Pietsch Eva-Christine Weiss Evelyn Jantscher-Krenn Christine Moissl-Eichinger
author_sort	Manuela-Raluca Pausan
title	Human Milk Oligosaccharides Modulate the Risk for Preterm Birth in a Microbiome-Dependent and -Independent Manner
title_short	Human Milk Oligosaccharides Modulate the Risk for Preterm Birth in a Microbiome-Dependent and -Independent Manner
title_full	Human Milk Oligosaccharides Modulate the Risk for Preterm Birth in a Microbiome-Dependent and -Independent Manner
title_fullStr	Human Milk Oligosaccharides Modulate the Risk for Preterm Birth in a Microbiome-Dependent and -Independent Manner
title_full_unstemmed	Human Milk Oligosaccharides Modulate the Risk for Preterm Birth in a Microbiome-Dependent and -Independent Manner
title_sort	human milk oligosaccharides modulate the risk for preterm birth in a microbiome-dependent and -independent manner
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/ce1160942cce4df1847ce02c6c86ac50
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Human Milk Oligosaccharides Modulate the Risk for Preterm Birth in a Microbiome-Dependent and -Independent Manner

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