Human milk oligosaccharides, antimicrobial drugs, and the gut microbiota of term neonates: observations from the KOALA birth cohort study

Abstract

The infant gut microbiota affects childhood health. This pioneer microbiota may be vulnerable to antibiotic exposures, but could be supported by prebiotic oligosaccharides found in breast milk and some infant formulas. We sought to characterize the effects of several exposures on the neonatal gut microbiota, including human milk oligosaccharides (HMOs), galacto-oligosaccharides (GOS), and infant/maternal antimicrobial exposures. We profiled the stool microbiota of 1023 one-month-old infants from the KOALA Birth Cohort using 16S rRNA gene amplicon sequencing. We quantified 15 HMOs in breast milk from the mothers of 220 infants, using high-performance liquid chromatography-mass spectrometry. Both breastfeeding and antibiotic exposure decreased gut microbial diversity, but each was associated with contrasting shifts in microbiota composition. Other factors associated with microbiota composition included C-section, homebirth, siblings, and exposure to animals. Neither infant exposure to oral antifungals nor maternal exposure to antibiotics during pregnancy were associated with infant microbiota composition. Four distinct groups of breast milk HMO compositions were evident, corresponding to maternal Secretor status and Lewis group combinations defined by the presence/absence of certain fucosylated HMOs. However, we found the strongest evidence for microbiota associations between two non-fucosylated HMOs: 6’-sialyllactose (6’-SL) and lacto-N-hexaose (LNH), which were associated with lower and higher relative abundances of Bifidobacterium , respectively. Among 111 exclusively formula-fed infants, the GOS-supplemented formula was associated with a lower relative abundance of Clostridium perfringens . In conclusion, the gut microbiota is sensitive to some prebiotic and antibiotic exposures during early infancy and understanding their effects could inform future strategies for safeguarding a health-promoting infant gut microbiota.

Sources of gut microbiota variation in a large longitudinal Finnish infant cohort

“…Parity was also associated with maternal gut microbiota composition. The effect of parity or older siblings on infant microbiota has been observed previously 2 , 17 , 18 , 45 and it is mainly believed to reflect the added microbial exposures from the older siblings. Recently, infants with older siblings were found to have a more mature gut microbiota at 1 year, which in turn was associated with a lower prevalence of food allergy.…”

Microbiota from human infants consuming secretors or non-secretors mothers’ milk impacts the gut and immune system in mice

“…It is possible that elevated abundance of Bifidobacteria that use short-chain HMOs might outcompete Akkermansia. Clostridium_sensu_stricto , a bacterium which had the highest abundance in MFM mice, has been positively associated with antibiotic exposure during infancy ( 46 ). Interestingly, HMOs supplementation in these mice significantly reduced the abundance of this microbe, suggesting a potential beneficial effect of HMOs in formula-fed infants.…”

Determinants of microbial colonization in the premature gut

“…A proof-of-concept study proved that HMOs selectively enrich the growth of beneficial bacteria, including Bifidobacterium and Bacteroides (Marcobal et al 2011 ). In a large-scale study of 1023 infants, HMOs showed natural variations and influenced the GM of infants (Barnett et al 2023 ). Lacto-N-hexaose and 6′-sialyllactose were positively and negatively associated with the abundance of Bifidobacterium , respectively (Barnett et al 2023 ).…”

“…In a large-scale study of 1023 infants, HMOs showed natural variations and influenced the GM of infants (Barnett et al 2023 ). Lacto-N-hexaose and 6′-sialyllactose were positively and negatively associated with the abundance of Bifidobacterium , respectively (Barnett et al 2023 ). Additionally, the variable composition of HMOs can be explained by maternal genotype, including the secretor (FUT2) and Lewis (FUT3) genes, which, notably, do not drive major differences in the GM between infants (Barnett et al 2023 ).…”

“…Lacto-N-hexaose and 6′-sialyllactose were positively and negatively associated with the abundance of Bifidobacterium , respectively (Barnett et al 2023 ). Additionally, the variable composition of HMOs can be explained by maternal genotype, including the secretor (FUT2) and Lewis (FUT3) genes, which, notably, do not drive major differences in the GM between infants (Barnett et al 2023 ). These results suggest various mechanisms related to HMOs are involved and that further research is needed.…”