Tuesday, March 10, 2015

The Impact of Breast Milk on Development of Infant Gut Microbiota

The American Academy of Pediatrics and the World Health Organization both recommend exclusive breastfeeding, meaning the use of breast milk as an infant's sole source of nutrition, for the first six months of life.  The benefits of breast milk, which contains all of the vitamins and nutrients a baby needs for the first months of life, have long been studied by researchers and promoted by physicians.  If new mothers choose to breastfeed their infants, breast milk is the main, or only, source of nutrition during a crucial development period of a baby's immune system.  Recent research has focused on the impact of breast milk on this development, specifically in regard to formation of an infant's gut microbiota and allergic phenotype.



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.

References:
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).

9 comments:

  1. I was interested in this post after reading many recent articles related to the human microbiome and microbes specifically present in the gut. Certain gut microbes have been linked to a better ability to fight off disease and infections, and some have even been associated with weight gain. The idea that breast milk influences the gut microbes in human infants makes sense, as it is the first nutrient source introduced to them following birth and is therefore likely to impact their previously sterile immune system. While the findings of the study summarized in this post point towards a positive impact of breast milk on influencing the intestinal barrier, I agree with Celia's critical analysis of the study. It would be helpful to have more long-term studies that focus on gut microbe development and perhaps allergy tolerance to see if breast milk influences humans beyond the infant stage.

    ReplyDelete
  2. Women always hear that breastfeeding is good for their child because it is natural, unlike processed baby formula. However, this post properly defends the argument that breastfeeding has a positive influence on a child's early development. One thing I found especially interesting was that infants tend to have microbiota similar to it's mother's cells that it was delivered from. This finding proves that every little process in pregnancy influences the child's development. I believe the studies in this article pave the way for new scientific research in human development and ways to prevent a child from developing a disorder or disease.

    ReplyDelete
  3. Women always hear that breastfeeding is good for their child because it is natural, unlike processed baby formula. However, this post properly defends the argument that breastfeeding has a positive influence on a child's early development. One thing I found especially interesting was that infants tend to have microbiota similar to it's mother's cells that it was delivered from. This finding proves that every little process in pregnancy influences the child's development. I believe the studies in this article pave the way for new scientific research in human development and ways to prevent a child from developing a disorder or disease.

    ReplyDelete
  4. I found this article to be really insightful and relevant considering the growing popularity of enriched baby formulas and surrogate breast-feeding for mothers that have trouble producing milk. It seems that this article would suggest that perhaps it is healthier for the child to be given milk, even if it must be from another mother, than to be fed solely on formula. It would be interesting to look into whether children given milk from a mother other than their own would have a more diverse range of gut microbiota and a higher allergy tolerance.

    ReplyDelete
  5. This article was interesting in that it gave evidence that breastfeeding is actually beneficial towards infant growth and maturation. I was especially fascinated by the impact breast milk has on the gut microbiota. There are other regions in the body, however, where bacteria reside, such as the urinary tract, reproductive tract, skin, etc. It would be interesting to see further research questioning whether breast milk plays a role in determining the microbiota fauna in those areas as well as the gut.

    ReplyDelete
  6. I was really interested in this article because it provided a lot of insight into breastfeeding that I had never considered before. I understand the idea that children breastfed from a surrogate mother might have a better variety of gut microbiota. However, if an infant is born with a first introduction of their mother's vaginal/skin surface microbiota, then couldn't there be an adverse reaction to someone else's breast milk antibodies? It would also be interesting to see if surrogate breastfeeding may be able to prevent certain allergies that are suspected to be passed down through breastfeeding.

    ReplyDelete
  7. I found the idea that your gut microbiota reflects your method of birth very interesting. There is increasing evidence that the composition of your gut microbiota can continue to impact your health throughout life, and I wonder if the composition of your microbiota that reflects your method of birth stays with you throughout life or if it changes over time with maturation.

    ReplyDelete
  8. This post explains that the Rogier et al study found that breast milk may enhance the intestinal barrier, which piqued my interest because I wrote my blog post on HIV's effects on gut microbiota. HIV has been linked to a weakened intestinal barrier, which allows microbiota to leak into the bloodstream and further contribute to the disease by causing chronic immune activation. I wonder if HIV patients that were fed breastmilk as infants are less vulnerable to this complication than HIV patients that were not.

    ReplyDelete
  9. I think this post is especially relevant at a time like this, when many mothers are working, and returning to work fairly shortly after childbirth. As such they may be more likely to opt for formula, however, I think that it is very important women are informed on the serious benefits of breastfeeding and know that the decision between even storing breast milk and formula is not unimportant.

    ReplyDelete