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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 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.

SUBMITTER: Pausan MR

PROVIDER: S-EPMC7289590 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe etiology of preterm birth (PTB) is heterogeneous and not yet well known. Maternal periodontal disease has been investigated for decades and is a known risk factor for adverse pregnancy outcomes. However, no particular bacterial species or higher taxonomic order has been found as causative of PTB, leading to studies of the whole oral microbiome. In order to determine if and how the composition of the oral microbiome is associated with PTB, we performed a large case-control study including women with term (TB) and PTB.MethodsWe compared oral microbiomes in PTB to TB, to examine differences in the microbial richness, diversity, and differential abundance of specific taxa. We obtained oral swab samples from 152 Caucasian pregnant women who were classified as either PTB (≤36 6/7 weeks, n = 61) or TB (≥38 0/7 weeks, n = 91) in exclusion of any other major medical or obstetric conditions. The oral microbiomes of these women were characterized by 16S ribosomal RNA (rRNA) gene sequencing of the V3-V4 region on the MiSeq platform.ResultsThe dominant microorganisms at the phylum level in all pregnant women regardless of birth week outcomes as belonging to Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria, and Actinobacteria. The phyla Firmicutes and Bacteroidetes were relatively more abundant in women with a PTB than in women with a TB, while Proteobacteria was less prevalent in women with a PTB. At the genus level, Veillonella, Prevotella, and Capnocytophaga were enriched in the PTB, and while many of the members of these genera could not be resolved to the species level, Veillonella massillensis was shown to be increased in the PTB group.ConclusionWe identified the genera Veillonella, Prevotella, and Capnocytophaga in the maternal oral microbiome as being associated with PTB independently of clinically apparent infection, uterine anomalies, and other pregnancy complications, including placenta previa, and placental abruption. The clarification of the role of those taxa in the etiology of PTB merits further research.

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

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