Direct breastfeeding increases the transfer of microorganisms to the gut of very low birth weight infants.

New research shows that direct breastfeeding enhances the transfer of beneficial microorganisms from breast milk to very low birth weight infants, even in the face of antibiotic use, helping shape the infant’s gut microbiome and potentially improving long-term health outcomes.

Study: Breastmilk microbiota is associated with developing gut microbial consortia in very low birth weight infants. Photo credit: Kateryna Kon / Shutterstock

In a longitudinal cohort study published in the journal Cellular Reports Medicine, Researchers in Canada have investigated the relationship between microorganisms in preterm infant milk and the gut microbiota of very low birth weight (VLBW) infants during their initial hospital stay.

They found that approximately 30–40% of the gut microbiota of very low-birth-weight infants was composed of microbes shared between breast milk and infant stool. Furthermore, these relationships were found to be influenced by feeding practices, the postnatal period, and antibiotic use, with a dose-response relationship, where higher intakes of microorganisms from breast milk resulted in higher concentrations of bacteria in the infant gut.

Background

VLBW preterm infants often develop abnormal gut bacterial communities, leading to conditions such as necrotizing enterocolitis and late-onset sepsis. Breast milk with beneficial bacteria, human milk oligosaccharides (HMOs), and bioactive proteins reduces these risks and improves neurodevelopment.

While studies of healthy term infants show that bacteria in breast milk help establish the gut microbiota, these findings may not apply to very low-birth-weight infants. Very low-birth-weight infants face unique challenges, including frequent use of antibiotics, limited breastfeeding opportunities, and reliance on pumped and pasteurized donor milk that lacks viable bacteria. These factors, along with nutrient fortification, alter the microbial and nutritional environment provided to the infant.

No studies to date have directly examined the association between breast milk bacterial communities and gut colonization in very-low-birth-weight infants, so it is important to investigate how these specific conditions impact infant gut health.

Therefore, the researchers in the present study investigated the association between the milk microbiota of preterm infants and the gut microbiota of very low birth weight infants and also investigated the influence of feeding practices, in particular the influence of direct breastfeeding, antibiotic exposure and the postnatal period.

About the study

A total of 94 mother-infant pairs were enrolled in the OptiMoM booster study. Infants born <1250 grams were eligible for the study, with a mean birth weight of 850 grams and a median gestational age of 27.4 weeks. Infants with congenital anomalies and previously formula-fed were excluded. Approximately 67% of infants were primarily breastfed, 33% were formula-fed, and 54.3% were breastfed. Probiotics were not used, and 84% of infants were breastfed before hospital discharge, starting at a median postmenstrual age of 34 weeks.

Data on maternal and infant characteristics were collected, and breast milk samples were collected according to hygienic practices. Weekly stool samples were collected from infants and paired with a sample of related milk over seven days for analysis (n = 422 pairs).

Deoxyribonucleic acid (DNA) was extracted from milk and feces samples for 16S ribonucleic acid (rRNA) sequencing to assess microbial communities.

Hospital feeding variables were categorized based on percentage of breast milk, type of fortifier, and whether breastfeeding occurred. Sequencing data were cleaned and processed to create zero-radius operational taxonomic units (zOTUs). Contaminants were removed, data were aligned, and a phylogenetic tree was constructed for analysis using bioinformatics tools.

Results and discussion

A total of 2308 zOTUs were found in breast milk. The number of zOTUs and microbial diversity in breast milk decreased over time, while in infant stool it increased (p<0.001).

Only 7.4% of zOTUs were shared between breast milk and infant stool samples, representing 60 genera. Direct breastfeeding significantly increased the likelihood of sharing bacteria, such as Weillonella, StreptococcusAND Haemophiliawhich suggests that direct breastfeeding plays a key role in improving the transfer of microorganisms to the infant gut.

Distinct microbial community structures were observed in breast milk and infant stool, which became increasingly different over time, mainly due to differences in bacterial abundance.

Feeding type, fortifier (human or bovine), and postnatal period influenced patterns of bacterial transmission and diversity. The study found dose-response relationships between the amount of bacteria ingested in breast milk and microbial concentrations in the infant gut, particularly for bacteria such as Veillonella, streptococcusAND Clostridium sensu stricto.

Antibiotic use had a significant effect, with 92.6% of infants and 59.8% of mothers receiving antibiotics. Both maternal and infant antibiotic exposure modified these microbial relationships. Mother-infant pairs with low antibiotic exposure (<1 day for mothers and <3 days for infants) showed stronger correlations between milk bacterial intake and infant gut microbiota composition, whereas those with higher antibiotic exposure had more impaired microbial transmission.

The study found clear dose-response relationships between specific bacteria in breast milk and their concentrations in infant stool. Higher milk consumption was directly correlated with greater microbial diversity in the infant gut, with direct breastfeeding and milk consumption shaping the infant gut microbiota.

Overall, the results underscore the importance of breastfeeding and feeding practices in influencing the development of the infant gut microbiota. The study is strengthened by the use of standardized abundance data, detailed daily feeding records, and weekly paired milk and stool samples to capture temporal trends in the microbiota.

However, the study is limited by the lack of use of 16S rRNA gene sequencing to distinguish viable bacteria or confirm transmission at the strain level, difficulties with metagenomic sequencing, and the unexplored impact of different types of antibiotics on the relationship between the gut and milk microbiome.

Application

This study indicates that the association between breast milk microbiota and the gut microbiota of very low birth weight infants is dose-dependent and influenced by the postnatal period, feeding practices, direct breastfeeding, and antibiotic exposure.

Research suggests that breast milk can help shape the intestinal microflora of very low-birth-weight infants, which may have a positive impact on their health.

These results support the promotion of direct breastfeeding during hospitalization and improved antibiotic stewardship. They may also help develop future microbial therapies, such as probiotics and postbiotics, tailored to the needs of very low birth weight infants.