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.

Figure 1

Representative ¹H NMR spectra of the aqueous fraction of breast milk. 1, LNDFHII; 2, α1–3 fucosyllated oligosaccharides; 3, α1–2 fucosyllated oligosaccharides; 4, α1–4 fucosyllated oligosaccharides; 5, lactate; 6, Leucine/isoleucine; 7, 6′-sialyllactose; 8, 3′-sialyllactose; 9 and 10, N-acetylglucosamine containing oligosaccharides; 11, glutamine; 12, glutamate; 13, citrate; 14, creatine; 15, creatinine; 16, choline; 17, phosphocholine; 18, glycerophosphocholine; 19, lactose; 20, Taurine; 21, glucose/glucose containing oligosaccharides; 22, oligosaccharides containing GlcNAc(β1–6) linkage; 23, LNFPIII and branched chain oligosaccharides; 24, LNDFHI and branched chain oligosaccharides. Adapted with permission from Erney et al.

Figure 2

Comparison of spectra of mothers producing different profiles of HMOs. Spectra from mothers in blue, orange and red are non-Secretors, as these spectra do not contain signals corresponding to 2′-FL between δ 1.22 and 1.25, while the mothers in green and black are classified as Secretors.

Figure 3

Three overlaid ¹H NMR spectra from the aqueous fraction of breast milk originating from the same mother collected at 1 day postpartum (black), 6 days postpartum (blue) and 3 months postpartum (red).