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. 1H 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 (X2 = 12.50, Po0.001). Infants of
Lewis-positive mothers were less likely GBS colonised at birth (X2 = 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.