Dataset Information

Role of human milk oligosaccharides in Group B Streptococcus colonisation.

ABSTRACT: Group B Streptococcus (GBS) infection is a major cause of morbidity and mortality in infants. The major risk factor for GBS disease is maternal and subsequent infant colonisation. It is unknown whether human milk oligosaccharides (HMOs) protect against GBS colonisation. HMO production is genetically determined and linked to the Lewis antigen system. We aimed to investigate the association between HMOs and infant GBS colonisation between birth and postnatal day 90. Rectovaginal swabs were collected at delivery, as well as colostrum/breast milk, infant nasopharyngeal and rectal swabs at birth, 6 days and days 60-89 postpartum from 183 Gambian mother/infant pairs. GBS colonisation and serotypes were determined using culture and PCR. (1)H nuclear magnetic resonance spectroscopy was used to characterise the mother's Lewis status and HMO profile in breast milk. Mothers who were Lewis-positive were significantly less likely to be colonised by GBS (X (2)=12.50, P<0.001). Infants of Lewis-positive mothers were less likely GBS colonised at birth (X (2)=4.88 P=0.03) and more likely to clear colonisation between birth and days 60-89 than infants born to Lewis-negative women (P=0.05). There was no association between Secretor status and GBS colonisation. In vitro work revealed that lacto-N-difucohexaose I (LNDFHI) correlated with a reduction in the growth of GBS. Our results suggest that HMO such as LNDFHI may be a useful adjunct in reducing maternal and infant colonisation and hence invasive GBS disease. Secretor status offers utility as a stratification variable in GBS clinical trials.

SUBMITTER: Andreas NJ

PROVIDER: S-EPMC5007626 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Role of human milk oligosaccharides in Group B Streptococcus colonisation.

Andreas Nicholas J NJ Al-Khalidi Asmaa A Jaiteh Mustapha M Clarke Edward E Hyde Matthew J MJ Modi Neena N Holmes Elaine E Kampmann Beate B Mehring Le Doare Kirsty K

Clinical & translational immunology 20160826 8

Group B Streptococcus (GBS) infection is a major cause of morbidity and mortality in infants. The major risk factor for GBS disease is maternal and subsequent infant colonisation. It is unknown whether human milk oligosaccharides (HMOs) protect against GBS colonisation. HMO production is genetically determined and linked to the Lewis antigen system. We aimed to investigate the association between HMOs and infant GBS colonisation between birth and postnatal day 90. Rectovaginal swabs were collect ...[more]

PMID: 27588204

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Project description: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. In addition, 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. IMPORTANCE 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. Current recommended prophylaxis consists of administering broad-spectrum antibiotics to GBS-positive mothers during labor. Although antibiotics have significantly reduced GBS neonatal disease, there are several unintended consequences, including altered neonatal gut bacteria and increased risk for other types of infection. Innovative preventions displaying more targeted antimicrobial activity, while leaving the maternal microbiota intact, are thus appealing. Using a mouse model, we found that human milk oligosaccharides (HMOs) reduce GBS burdens without perturbing the vaginal microbiota. We conclude that HMOs are a promising alternative to antibiotics to reduce GBS neonatal disease.

Project description:The prevalence and incidence of allergic diseases is rising and these diseases have become the most common chronic diseases during childhood in Westernized countries. Early life forms a critical window predisposing for health or disease. Therefore, this can also be a window of opportunity for allergy prevention. Postnatally the gut needs to mature, and the microbiome is built which further drives the training of infant's immune system. Immunomodulatory components in breastmilk protect the infant in this crucial period by; providing nutrients that contain substrates for the microbiome, supporting intestinal barrier function, protecting against pathogenic infections, enhancing immune development and facilitating immune tolerance. The presence of a diverse human milk oligosaccharide (HMOS) mixture, containing several types of functional groups, points to engagement in several mechanisms related to immune and microbiome maturation in the infant's gastrointestinal tract. In recent years, several pathways impacted by HMOS have been elucidated, including their capacity to; fortify the microbiome composition, enhance production of short chain fatty acids, bind directly to pathogens and interact directly with the intestinal epithelium and immune cells. The exact mechanisms underlying the immune protective effects have not been fully elucidated yet. We hypothesize that HMOS may be involved in and can be utilized to provide protection from developing allergic diseases at a young age. In this review, we highlight several pathways involved in the immunomodulatory effects of HMOS and the potential role in prevention of allergic diseases. Recent studies have proposed possible mechanisms through which HMOS may contribute, either directly or indirectly, via microbiome modification, to induce oral tolerance. Future research should focus on the identification of specific pathways by which individual HMOS structures exert protective actions and thereby contribute to the capacity of the authentic HMOS mixture in early life allergy prevention.

Dataset Information

Role of human milk oligosaccharides in Group B Streptococcus colonisation.

Publications

Role of human milk oligosaccharides in Group B Streptococcus colonisation.

Similar Datasets

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