An infant's gastrointestinal tract is sterile prior to birth, receiving its first introduction to microbes from its mother. Interestingly, previous studies have shown that vaginally delivered infants have microbiota resembling the vaginal microbiota of their mothers, while infants delivered via Caesarian section have microbiota resembling their mother's skin surface microbiota. After this first introduction, the simple microbiota of infants develop into a highly diverse and comprehensive adult microbiota, influenced by both environment and innate factors.
Rogier et al postulate that one of the innate factors that influences microbiota development is exposure to breast milk. This hypothesis is based on evidence that breast milk provides antigen-specific immunity to infants and studies that show that the microbiota of breast-fed and formula-fed infants differ significantly. Breast milk contains a variety of antibodies, most predominantly IgA. The pIgR receptor transports IgA across mammary gland epithelial cells via attachment to its extracellular domain, the secretory component. This attachment protects IgA from degradation by proteases and other enzymes. Because IgA antibodies target specific microbes in the gastrointestinal tract of its host, a woman's breast milk contains antibodies against the microbes most prominent in her gastrointestinal tract, which are those most likely to be present in her infant.
In order to test whether or not breast milk regulates the composition of an infant's microbiota, Rogier et al developed a mouse model to separately study the effects of IgA derived from breast milk and IgA produced endogenously. This was done by making a targeted deletion in the Pigr gene, preventing the mice from transporting IgA into milk for their offspring. The microbiota of these offspring and the microbiota of the offspring of control mice were then studied. Several important results were found from this examination. The mice that failed to receive IgA from breast milk had an increased amount of bacteria in the mesenteric lymph nodes, indicating a breach of the intestinal barrier. This indicates that breast milk enhances this intestinal barrier, preventing bacteria translocation. The study also showed that the differences between mice that received breast milk and those that did not were important in adulthood. This was supported by differences in adult microbiota of mice that received maternal IgA and mice that did not, which had differing abundances of bacteria from one another. In fact, the gut microbiota of adult mice that did not receive maternal IgA had a higher amount of Pasteurellaceae and Lachnospiraceae, two bacteria common in patients with inflammatory bowel disease.
Figure 1: Hypothesis of Role of IgA in Development of Infant Immunity
Rogier E, Frantz A, Bruno M, Wedlund L, Cohen D, Stromberg A, Kaetzel C. Lessons from mother: Long-term impact of antibodies in breast milk on the gut microbiota and intestinal immune system of breastfed offspring. Gut Microbes, 5:(5) 663-668 (2014).
The influence of breast milk on infant development extends beyond the composition of gut microbiota. Hochwallner et al provide evidence that a mother's allergen-specific antibodies are transported from her blood to her breast milk, thus reaching her baby via breastfeeding. This information supports the idea that breast milk can influence the allergy phenotype of an infant. A study done by Munblit et al also focuses on allergies, giving a summary of the research on this topic. The overview states, however, that the evidence for a connection between breastfeeding and allergic sensitization is contradictory. Due to large inconsistencies in experimental design and data collection across studies, the influence of breast milk on infants is still largely unclear.
The research presented here on breastfeeding provides evidence that allows us to conclude that breast milk has some influence on infant development, and that this influence is probably positive. There are, however, many opportunities for further research to understand this connection more clearly. The mechanism of IgA, for example, needs to be understood in order to determine why maternal IgA enhances the intestinal barrier. Once this is understood, it may be possible to develop a formula that gives formula-fed infants the same intestinal protection as those that are breast-fed. In addition, before conclusions can be drawn about breastfeeding and allergy development, several long-term, controlled studies need to be undertaken. At this point, a lack of these studies demotes any conclusion to mere speculation.
1. Hochwallner H, Alm J, Lupinek C, Johansson C, Mie A, Scheynius A, Valenta R. Transmission of allergen-specific IgG and IgE from maternal blood into breast milk visualized with microarray technology. J Allergy Clin Immunol, 135:(5) 1213-1215 (2014).
2. Munblit D, Boyle R, Warner J. Factors affecting breast milk composition and potential consequences for development of the allergic phenotype. Clinical and Experimenal Allergy, (45) 583-601 (2014).
3. Rogier E, Frantz A, Bruno M, Wedlund L, Cohen D, Stromberg A, Kaetzel C. Lessons from mother: Long-term impact of antibodies in breast milk on the gut microbiota and intestinal immune system of breastfed offspring. Gut Microbes, 5:(5) 663-668 (2014).