scholarly journals Human Milk Oligosaccharides Reduce Murine Group B Streptococcus Vaginal Colonization with Minimal Impact on the Vaginal Microbiota

mSphere ◽  
2022 ◽  
Author(s):  
Marlyd E. Mejia ◽  
Samantha Ottinger ◽  
Alison Vrbanac ◽  
Priyanka Babu ◽  
Jacob J. Zulk ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Human Milk ◽  
Group B Streptococcus ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Minimal Impact ◽  
Vaginal Colonization ◽  
Fetal Infection ◽  
Serious Disease ◽  
Group B

During pregnancy, GBS ascension into the uterus can cause fetal infection or preterm birth. In addition, GBS exposure during labor creates a risk of serious disease in the vulnerable newborn and mother postpartum.

scholarly journals Role of human milk oligosaccharides in Group B Streptococcus colonisation

2016 ◽  
Vol 5 (8) ◽  
pp. e99 ◽  
Author(s):  
Nicholas J Andreas ◽  
Asmaa Al-Khalidi ◽  
Mustapha Jaiteh ◽  
Edward Clarke ◽  
Matthew J Hyde ◽  
...  
Keyword(s):  
Human Milk ◽  
Group B Streptococcus ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Group B

scholarly journals A Solution to Antifolate Resistance in Group B Streptococcus: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Schuyler A. Chambers ◽  
Rebecca E. Moore ◽  
Kelly M. Craft ◽  
Harrison C. Thomas ◽  
Rishub Das ◽  
...  
Keyword(s):  
Human Milk ◽  
Metabolic Response ◽  
Group B Streptococcus ◽  
Resistance Mechanisms ◽  
Human Milk Oligosaccharides ◽  
Intrinsic Resistance ◽  
Milk Oligosaccharides ◽  
Content Type ◽  
Ultrahigh Performance Liquid Chromatography ◽  
Group B

ABSTRACT Adjuvants can be used to potentiate the function of antibiotics whose efficacy has been reduced by acquired or intrinsic resistance. In the present study, we discovered that human milk oligosaccharides (HMOs) sensitize strains of group B Streptococcus (GBS) to trimethoprim (TMP), an antibiotic to which GBS is intrinsically resistant. Reductions in the MIC of TMP reached as high as 512-fold across a diverse panel of isolates. To better understand HMOs’ mechanism of action, we characterized the metabolic response of GBS to HMO treatment using ultrahigh-performance liquid chromatography–high-resolution tandem mass spectrometry (UPLC-HRMS/MS) analysis. These data showed that when challenged by HMOs, GBS undergoes significant perturbations in metabolic pathways related to the biosynthesis and incorporation of macromolecules involved in membrane construction. This study represents reports the metabolic characterization of a cell that is perturbed by HMOs. IMPORTANCE Group B Streptococcus is an important human pathogen that causes serious infections during pregnancy which can lead to chorioamnionitis, funisitis, premature rupture of gestational membranes, preterm birth, neonatal sepsis, and death. GBS is evolving antimicrobial resistance mechanisms, and the work presented in this paper provides evidence that prebiotics such as human milk oligosaccharides can act as adjuvants to restore the utility of antibiotics.

scholarly journals Human milk oligosaccharides reduce murine group B Streptococcus vaginal colonization with minimal impact on the vaginal microbiota

2021 ◽  
Author(s):  
Marlyd E Mejia ◽  
Samantha Ottinger ◽  
Alison Vrbanac ◽  
Priyanka Babu ◽  
Jacob Zulk ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Milk ◽  
Biofilm Formation ◽  
Group B Streptococcus ◽  
Human Milk Oligosaccharides ◽  
Vaginal Colonization ◽  
Vaginal Epithelial Cells ◽  
Group B

Group B Streptococcus (GBS) colonizes the vaginal mucosa of a significant percentage of healthy women and is a leading cause of neonatal bacterial infections. Currently, pregnant women are screened in the last month of pregnancy and GBS-positive women are given antibiotics during parturition to prevent bacterial transmission to the neonate. Recently, human milk oligosaccharides (HMOs) isolated from breastmilk were found to inhibit GBS growth and biofilm formation in vitro, and women that make certain HMOs are less likely to be vaginally colonized with GBS. Using in vitro human vaginal epithelial cells and a murine vaginal colonization model, we tested the impact of HMO treatment on GBS burdens and the composition of the endogenous microbiota by 16S rRNA amplicon sequencing. HMO treatment reduced GBS vaginal burdens in vivo with minimal alterations to the vaginal microbiota. HMOs displayed potent inhibitory activity against GBS in vitro, but HMO pretreatment did not alter adherence of GBS or the probiotic Lactobacillus rhamnosus to human vaginal epithelial cells. Additionally, disruption of a putative GBS glycosyltransferase (Δsan_0913) rendered the bacterium largely resistant to HMO inhibition in vitro and in vivo but did not compromise its adherence, colonization, or biofilm formation in the absence of HMOs. We conclude that HMOs are a promising therapeutic bioactive to limit GBS vaginal colonization with minimal impacts on the vaginal microenvironment.

scholarly journals Human Milk Oligosaccharides modulate the risk for preterm birth in a microbiome dependent and independent manner

2019 ◽  
Author(s):  
Manuela-Raluca Pausan ◽  
Vassiliki Kolovetsiou-Kreiner ◽  
Gesa Lucia Richter ◽  
Tobias Madl ◽  
Elisabeth Giselbrecht ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Human Milk ◽  
Sterile Inflammation ◽  
Human Milk Oligosaccharides ◽  
Spontaneous Preterm Birth ◽  
Milk Oligosaccharides ◽  
Short Cervix ◽  
Independent Manner ◽  
Cross Sectional ◽  
Urinary Microbiome

AbstractBackgroundPreterm birth is one of the leading causes of neonatal mortality. The causes for spontaneous preterm birth (PTB) are multifactorial and remain often 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 and without preterm labor and correlated our findings with measurements of metabolites and HMOs in urine and blood.ResultsWe identified several microbial signatures associated with short cervix, PTB and/or preterm contractions such asLactobacillus jensenii,L. gasseri,Ureaplasma sp. andGardnerella sp..Additionally, 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.ConclusionsIdentifying 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, potentially driven by secretor-active HMOs in urine. Our results support current efforts to improve diagnostics and therapeutic strategies.

scholarly journals Human Milk Oligosaccharides to Prevent Gut Dysfunction and Necrotizing Enterocolitis in Preterm Neonates

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1461 ◽  
Author(s):  
Stine Bering
Keyword(s):  
Preterm Birth ◽  
Human Milk ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Bacterial Colonization ◽  
Health Benefits ◽  
Preterm Neonates ◽  
Human Milk Oligosaccharides ◽  
High Concentration ◽  
Milk Oligosaccharides

This review focuses on the evidence for health benefits of human milk oligosaccharides (HMOs) for preterm infants to stimulate gut adaptation and reduce the incidence of necrotizing enterocolitis (NEC) in early life. The health benefits of breastfeeding are partly explained by the abundant HMOs that serve as prebiotics and immunomodulators. Gut immaturity in preterm infants leads to difficulties in tolerating enteral feeding and bacterial colonization and a high sensitivity to NEC, particularly when breast milk is insufficient. Due to the immaturity of the preterm infants, their response to HMOs could be different from that in term infants. The concentration of HMOs in human milk is highly variable and there is no evidence to support a specifically adapted high concentration in preterm milk. Further, the gut microbiota is not only different but also highly variable after preterm birth. Studies in pigs as models for preterm infants indicate that HMO supplementation to formula does not mature the gut or prevent NEC during the first weeks after preterm birth and the effects may depend on a certain stage of gut maturity. Supplemented HMOs may become more important for gut protection in the preterm infants when the gut has reached a more mature phase.

scholarly journals Human Milk Oligosaccharides Exhibit Biofilm Eradication Activity Against Matured Biofilms Formed by Different Pathogen Species

2022 ◽  
Vol 12 ◽  
Author(s):  
Sylwia Jarzynka ◽  
Riccardo Spott ◽  
Tinatini Tchatchiashvili ◽  
Nico Ueberschaar ◽  
Mark Grevsen Martinet ◽  
...  
Keyword(s):  
Human Milk ◽  
Pathogenic Bacteria ◽  
Biological Significance ◽  
Burkholderia Cenocepacia ◽  
Respiratory Pathogens ◽  
Human Milk Oligosaccharides ◽  
Group B Streptococci ◽  
Milk Oligosaccharides ◽  
Gram Positive ◽  
Group B

Human milk oligosaccharides (HMOs) have been shown to exhibit plenty of benefits for infants, such as prebiotic activity shaping the gut microbiota and immunomodulatory and anti-inflammatory activity. For some pathogenic bacteria, antimicrobial activity has been proved, but most studies focus on group B streptococci. In the present study, we investigated the antimicrobial and antibiofilm activities of the total and fractionated HMOs from pooled human milk against four common human pathogenic Gram-negative species (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Burkholderia cenocepacia) and three Gram-positive species (Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis). The activity of HMOs against enterococci and B. cenocepacia are addressed here for the first time. We showed that HMOs exhibit a predominant activity against the Gram-positive species, with E. faecalis being the most sensitive to the HMOs, both in planktonic bacteria and in biofilms. In further tests, we could exclude fucosyllactose as the antibacterial component. The biological significance of these findings may lie in the prevention of skin infections of the mother’s breast as a consequence of breastfeeding-induced skin laceration and/or protection of the infants’ nasopharynx and lung from respiratory pathogens such as staphylococci.

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

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Manuela-Raluca Pausan ◽  
Vassiliki Kolovetsiou-Kreiner ◽  
Gesa Lucia Richter ◽  
Tobias Madl ◽  
Elisabeth Giselbrecht ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Human Milk ◽  
Sterile Inflammation ◽  
Vaginal Microbiome ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Short Cervix ◽  
Independent Manner ◽  
Cross Sectional ◽  
Content Type

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.

scholarly journals Group B Streptococcus CAMP Factor Does Not Contribute to Interactions with the Vaginal Epithelium and Is Dispensable for Vaginal Colonization in Mice

2021 ◽  
Author(s):  
Mallory B. Ballard ◽  
Vicki Mercado-Evans ◽  
Madelynn G. Marunde ◽  
Hephzibah Nwanosike ◽  
Jacob Zulk ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Antibiotic Prophylaxis ◽  
Pregnant Women ◽  
Group B Streptococcus ◽  
Vaginal Epithelium ◽  
Content Type ◽  
Vaginal Colonization ◽  
Camp Factor ◽  
Intrapartum Antibiotic ◽  
Group B

Group B Streptococcus (GBS) remains a pervasive pathogen for pregnant women and their newborns. Maternal screening and intrapartum antibiotic prophylaxis to GBS-positive mothers have reduced, but not eliminated GBS neonatal disease, and have not impacted GBS-associated preterm birth or stillbirth.

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