New research shows that direct breastfeeding strengthens the transfer of beneficial microbes from mother’s milk to very-low-birth-weight infants, even in the face of antibiotic use, helping shape the infant gut microbiome and potentially improving long-term health outcomes.
Study: Mother’s milk microbiota is associated with the developing gut microbial consortia in very-low-birth-weight infants. Image Credit: Kateryna Kon / Shutterstock
In a longitudinal cohort study published in the journal Cell Reports Medicine, researchers from Canada analyzed the relationship between the microbes in preterm mothers’ milk and the gut microbiota of very-low-birth-weight (VLBW) infants across their initial hospitalization.
They found that about 30–40% of the microbiota in the VLBW infant's gut were formed by the microbes shared between the mother’s milk and infant stools. Further, these relationships were found to be influenced by feeding practices, the postnatal period, and antibiotic use, with a notable dose-response relationship, where higher microbial intake from the mother's milk resulted in higher bacterial concentrations in the infant's gut.
Background
Preterm VLBW infants often develop abnormal gut bacterial communities, leading to conditions like necrotizing enterocolitis and late-onset sepsis. Mother’s milk, with its beneficial bacteria, human milk oligosaccharides (HMOs), and bioactive proteins, reduces these risks and improves neurodevelopment.
While studies in healthy term infants show that bacteria in mother’s milk help establish gut microbiota, these findings may not apply to VLBW infants. VLBW infants experience unique challenges, including frequent antibiotic use, limited ability to feed at the breast, and reliance on pumped and pasteurized donor milk, which lacks live bacteria. These factors, along with nutrient fortification of milk, alter the microbial and nutritional environment delivered to the infant.
None of the studies so far have directly examined the relationship between the bacterial communities in mother’s milk and gut colonization in VLBW infants, making it important to explore how these specific conditions impact infant gut health.
Therefore, researchers in the present study examined the relationship between microbiota in preterm mother’s milk and the gut microbiota of VLBW infants and investigated the effects of feeding practices, particularly the impact of direct breastfeeding, antibiotic exposure, and the postnatal period.
About the study
A total of 94 mother-infant pairs were included from the OptiMoM fortifier study. Infants born under 1250 grams were eligible for the study, with a median birth weight of 850 grams and a median gestational age of 27.4 weeks. Infants with congenital anomalies and previous formula feeding were excluded. About 67% of infants were primarily fed mother's milk, 33% received mixed feeds, and 54.3% were given human milk-based fortifiers. Probiotics were not used, and 84% of infants began breastfeeding before discharge, starting at a median postmenstrual age of 34 weeks.
Data on maternal and infant characteristics were collected, and the mother’s milk samples were obtained following hygienic practices. Weekly stool samples were collected from infants and paired with the cognate milk sample within a seven-day range for analysis (n = 422 pairs).
Deoxyribonucleic acid (DNA) was extracted from both milk and stool samples for 16S ribosomal ribonucleic acid (rRNA) sequencing to assess microbial communities.
In-hospital feeding variables were categorized based on the percentage of mothers' milk fed, the type of fortifier, and whether breastfeeding occurred. Sequencing data were cleaned and processed to create zero-radius operational taxonomic units (zOTUs). Contaminants were removed, the data were aligned, and a phylogenetic tree was constructed for analysis using bioinformatics tools.
Results and discussion
A total of 2,308 zOTUs were found in mother’s milk. The number of zOTUs and microbial diversity in mother’s milk decreased over time, while they increased in infant stools (p<0.001).
Only 7.4% of zOTUs were shared between mother’s milk and infant stool samples, mapping to 60 genera. Direct breastfeeding significantly increased the likelihood of sharing bacteria, such as Veillonella, Streptococcus, and Hemophilus, suggesting that direct breastfeeding plays a crucial role in enhancing microbial transfer to the infant's gut.
Distinct microbial community structures were observed between mother’s milk and infant stools, which diverged more over time, primarily due to differences in bacterial abundance.
The type of feeding, fortifier (human vs. bovine), and postnatal period influenced bacterial transmission and diversity patterns. The study revealed dose-response relationships between the amount of bacteria ingested via mother's milk and the microbial concentrations found in the infant's gut, particularly for bacteria such as Veillonella, Streptococcus, and Clostridium sensu stricto.
Antibiotic use had a significant impact, 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, while those with higher antibiotic exposure had more disrupted microbial transmission.
The study found clear dose-response relationships between specific bacteria in a mother’s milk and their concentrations in infant stools. Higher milk intake directly correlated with greater microbial diversity in the infant gut, with direct breastfeeding and milk intake shaping the infant gut microbiota.
Overall, the findings emphasize the importance of breastfeeding and feeding practices in influencing infant gut microbiota development. The study is strengthened by the use of normalized abundance data, detailed daily feeding records, and weekly paired milk-stool samples to capture temporal trends in microbiota.
However, the study is limited by the lack of use of 16S rRNA gene sequencing to distinguish viable bacteria or confirm strain-level transmission, challenges with metagenomic sequencing, and the unexamined impact of diverse antibiotic types on milk-gut microbiota relationships.
Conclusion
The present study suggests that the association between the microbiota in mother’s milk and the gut microbiota of VLBW infants is dose-dependent and influenced by the postnatal period, feeding practices, direct breastfeeding, and antibiotic exposure.
The findings suggest that mother’s milk may help shape the gut microbiota of VLBW infants, potentially improving their health outcomes.
These results support promoting direct breastfeeding during hospitalization and improving antibiotic stewardship and could inform the future development of microbial therapies, such as probiotics and postbiotics, tailored to benefit VLBW infants.