A Blog by Ed Yong

How Breast Milk Engineers a Baby’s Gut (and Gut Microbes)

Raising an infant is an act of ecosystem engineering. You’re not just caring for a baby, but an entire world.

Right from birth, babies are colonised by legions of microbes that set up shop in their guts, skin, and more. These are vital. They help the growing human to digest its food, and to keep harmful microbes away. They are so important that newborns temporarily suppress their own immune system to give their microbial partners a chance to establish themselves.

Mum helps too. Her vaginal secretions provide her child with a starter pack of microbes. And her breast milk contains special sugars that seem to selectively nourish the gut bacteria that infants need.

Now, Eric Rogier from the University of Kentucky has found a milk antibody called SIgA also helps to set up the right community of gut microbes. Without it, young mice face long-lasting consequences, including several signs of inflammatory bowel diseases (IBD).  This antibody sets up a healthier environment in an infant’s intestinal tract, so they’re better prepared to withstand environmental problems later in life,” says Charlotte Kaetzel, who led the study.

Although the team only looked at mice, Kaetzel notes that several studies have found that breastfed babies are less likely to develop IBD later in life. “We’re not talking about black and white: you’re protected if you’re breastfed and not protected if you aren’t,” she says. “But I’d certainly argue that there’s a clear benefit.”

“We now recognize more and more that factors in breast milk influence the gut microbiota, which in turn sets up the immune system to have fewer chronic illnesses later in life,” says Allan Walker from Massachusetts General Hospital.

Milk contains a vast cocktail of molecules, and immunoglobin A (IgA or SIgA) is one of them. It’s an antibody found in our bodily secretions. We manufacture it in ridiculous amounts: around a teaspoon every day. It’s in milk, mucus, tears, saliva—anywhere where our cells shunt fluid into the outside world. Run a finger along any surface of your body and if it ends up wet, it probably has SIgA on it.

Mice and humans eventually make SIgA for themselves but in our earliest days of life, mother’s milk is the only source of the antibody. When Rogier engineered mutant mice that couldn’t produce SIgA in their milk, he found that their pups grew up with peculiar guts. They harboured with different communities of gut bacteria, and had more of certain groups that are seen in the guts of IBD patients. And some of these microbes ended up in unexpected places.

As a mouse grows up, its gut microbes interact with its own gut cells to create a sealed barrier that keeps foreign material out of the deeper intestinal tissue. The barrier is a good fence that makes for good neighbours. But if newborn mice can’t get SIgA from their mothers, their intestinal barriers are porous and bacteria pass into the underlying lymph nodes.

“These lymph nodes should be absolutely sterile,” says Kaetzel. “When you take them out of an adult mouse and culture them, you’ll find no bacteria. When we took lymph nodes from offspring who didn’t get SIgA in their milk, they were loaded with bacteria.”

The most abundant species was Ochrobactrum anthropi—an opportunistic bacterium that’s been linked to a growing number of infections in hospital patients. It also depends on oxygen, which is odd since most gut bacteria shun the stuff or, at most, tolerate it. “You typically see overgrowth of aerobic bacteria when you have inflammation,” says Kaetzel.

“Beneficial bacteria in the intestinal tract are crucial, but you don’t necessarily want them around too much, like overgrowing in the lymph nodes,” says Katie Hinde from Harvard University. “This study shows that ingested SIgA is instrumental for limiting bacterial invasion beyond the gut wall.”

These early changes persisted into adulthood and left the mice permanently susceptible to inflammation, even if they could eventually make SIgA for themselves. When the team added an inflammatory chemical called DSS into their drinking water, those that didn’t get the antibody from their mothers reacted more vigorously. They strongly activated several genes that have been linked to IBD in humans.

When it comes to such diseases, scientists often talk about a triad of contributing factors: the host’s own biology, their microbes, and environmental factors like food-borne illnesses that can trigger inflammation. “These mice had altered two sides of this triangle,” says Kaetzel. They didn’t get enough SIgA (a host factor), and they ended up with strange microbiota. The DSS closed the triangle and led to severe inflammation.

The team now wants to see if it’s possible to boost the intestinal health of a formula-fed infant by supplementing them with SIgA, or even if the purified antibody could help older children or adults with intestinal problems.

And, of course, their study highlights yet another benefit to breastfeeding. It’s unique in isolating the effect of a single (major) ingredient of milk, but Kaetzel notes that breastfed infants also get a wide spectrum of other helpful substances.

For example, it contains its own microbes. Lisa Funkhouser and Seth Bordenstein have speculated that the lymphatic system conveys bacteria from a mother’s guts into her mammary glands, where they can be taken up by suckling infants.

If pups that don’t get SIgA from their mothers have weird bacteria in their lymph nodes, could they then pass on different microbes to their own offspring, when the time comes for them to produce milk? “There could be some really exciting transgenerational consequences from not ingesting sIgA in mother’s milk,” says Hinde.

Reference: Rogier, Frantz, Bruno, Wedlund, Cohen, Stromberg & Kaetzel. 2014. Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression. PNAS http://dx.doi.org/10.1073/pnas.1315792111

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29 thoughts on “How Breast Milk Engineers a Baby’s Gut (and Gut Microbes)

  1. How sure can we be about the similarity of mice and humans here? Other mammals are far more dependent on getting breast milk than humans are. Can we extrapolate from what happens to a mouse pup to what happens to a human baby?

  2. I was interested in your article and the transgenerational implications. In my parents generation, bottle feeding was the “in thing”. My generation began the switch to breast feeding. I am wondering if there is a connection to the prevalence of fibromyalgia and the transgenerational implications.

  3. Immunology is, arguably, the Cinderella of biomedical science. I welcome this study. I also welcome Matthew Herpers question. Challenge – always challenge. That is true science.

    I am a long-retired microbiologist who also has a lasting fascination with natural immune responses. More than 40 yrs ago I remarked that well-meant rules about food hygiene in particular, and hygiene in general, would result in greater numbers of allergies. The logic was, and remains, simple. An under-occupied (immune system) army attacks ever-lesser opponents, and becomes weaker itself, due to ever-diminishing challenges.

    Now look at the stats for asthma, food allergies etc.

  4. Mr. Herper, do you really think because many human infants have received baby formula over the course of the last 80 years or so that human babies have not evolved in a manner similar to all other mammals when it comes to consuming their mother’s milk? Oh my goodness!

  5. These studies on the effects of breastmilk/natural birth on the microbiome are interesting and definitely important. What I would love to see highlighted along with these are economics of breastfeeding–NOT the benefits to the economy if mothers breastfed (which is apparently a popular field of study), but how economics constrain people’s choices about breastfeeding. Ultimately, I would hope that coupling the biology and the economics will help bring more support for maternity/parental leave (I am writing from the U.S., which ranks near the bottom in support for paid parental leave). Let’s not leave this research to be just an interesting biological phenomenon (or a reason for guilt-tripping non-breastfeeding mothers), but a vehicle for positive change in society.

  6. No, Kim Sloan, I think there may be variation in how mammals use breast milk. There’s a lot of literature saying that while many mammals absorb antibodies from breast milk, primates (including people) don’t. See this reference: http://www.ncbi.nlm.nih.gov/pubmed/12850343?dopt=Abstract

    It’s always dangerous to assume that mice and people are alike. That led to lots of bad research in sepsis, for instance.

  7. Matthew, I’m not a trained scientist so I don’t pretend that I fully understand the full meaning of the study’s abstract but I’m reading this (copied directly from that abstract): ” Human milk also contains anti-idiotypic antibodies capable of enhancing infant antibody response. Maternal milk antibodies coat infant mucosal surfaces and some have a clear protective role. This has been studied extensively in infectious disease models such as rotavirus, E. coli, poliovirus, and retroviruses. In the rotavirus model, antirotaviral IgA can be detected in stools of breast-fed but not bottle-fed neonates.” to say that humans *do* absorb antibodies from Mother’s milk. I’m really not trying to start a fight, just trying to better understand your argument because I think this is a fascinating topic and one I would better like to understand. As a mother of 4 breastfed children, a breastfeeding support counselor, and a childbirth educator and doula, I have a personal interest in understanding what the evidence tells us about this topic so that I can best share that info with my clients and students. My experience certainly tells me that breastmilk boosts immunity but I would appreciate further input from your side of things.

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  9. Mr. Herper, I respect your comments regarding the differences in the immune systems of mice and humans, which are many. I would like to clarify one point. The purpose of SIgA in breast milk is not to be absorbed into the interior of the body, but rather to provide a protective layer in the lumen of the intestine that prevents microbes from invading the body. In fact, the reference you cite highlights the different protective mechanisms of antibodies that are absorbed vs. SIgA in the intestine. You may be interested in this review article: http://www.ncbi.nlm.nih.gov/pubmed/20105666?dopt=Citation

  10. So let’s go ahead and feed our babies powdered, hormone-filled cows milk formula that had vegetable oil as a main ingredient instead of the milk produced from their actual mother that is perfectly formulated for them. Makes sense.

  11. I wonder how antibiotics after weaning affect later IBDor IBS. Is there still a measurable difference in outcomes with breastfed and bottlefed people?

  12. Interesting link Matthew Herper. It does support the article though with saying that in humans the breast milk helps the gut from getting infected. I guess the exact mode isn’t accurate but the take home message is the same. Bottom line is that human milk is meant for a human infant and has evolved for such a purpose. Formula should only be a last resort. Milk banks and milk sharing should be utilised where breastfeeding/exclusive expressing isn’t possible.

  13. We don’t need studies in mice to tell us that human babies are protected from rotavirus and other infections by breastfeeding. We have a cluster-randomized study called the PROBIT study, conducted in Belarus, which also shows benefits on cognitive development. So yes, breast milk has real benefits over formula. But I didn’t ask that. I asked how easily we can extrapolate from a study of one mammal to another.

    Charlotte — that’s a very interesting paper. It partly answers my question. I still would be careful (as Ed was) extrapolating from this study to humans.

  14. What is unfortunate is that they don’t emphasize that this perfect system works only with vaginal birth, not c-sections. It is possible to somewhat colonize a newborn with mom’s bacteria by wiping the vagina w a tissue and then wiping the baby’s skin, or wiping the anus w a tissue then baby’s skin, but it will not be the same as baby coming through birth canal and having gut colonized by mouth. C-sections have been made out to be as almost a normal way to birth, which is just insane, and with lifelong health consequences and associated costs.

  15. One sentence stands out which I would like to comment on:
    “Other mammals are far more dependent on getting breast milk than humans are.” (M. Heper)
    Other mammals don’t have the option of using formula! And the use of formula for human babies is based primarily on the convenience (and lack of information) of the mom! That isn’t a health benefit, rather it is a cultural development which allows moms to be needed less by babies! Just because formula can be substituted for babies, doesn’t mean that it is just as healthy as breast milk; in fact, there are many studies that support the superiority of breast milk for human babies!

  16. Dai, I love your comment! Right on!
    “Let’s not leave this research to be just an interesting biological phenomenon (or a reason for guilt-tripping non-breastfeeding mothers), but a vehicle for positive change in society.”
    It would be fantastic if the U.S. would adopt the same parental leave policies that other First World countries already have. It would be an incredibly positive change for our nation.

    1. Great comment, Belle! The USA is far behind most highly developed nations in regards to social reforms such as parents’ leave policies, promotion of breast feeding (supported by the parents’ leave policies), health care issues, etc.

  17. Mr. Herper said: “… I think there may be variation in how mammals use breast milk. There’s a lot of literature saying that while many mammals absorb antibodies from breast milk, primates (including people) don’t. See this reference …”
    Mr. Herper, the article you sited does not state that primates do not absorb antibodies from mother’s milk. See the information on gut closure.

  18. I challenge everyone to actually read the ingredient label of infant formula before they espouse an opinion against breast milk. Would you feed your newborn, for instance, Similac (#1 Brand Fed in Hospitals!) if you know the #1 ingredient is corn syrup? That nearly all of the product is corn syrup and vegetable oils?

  19. In regard to Mike Sugar’s comment: Studies have shown in the past several years that what he says is true. For example, babies raised in completely spotless homes, who live in dust free environments, etc., development more allergies and the resulting sicknesses. Also, babies raised with pets in the home have fewer allergies. Some parents are so focused on not exposing their little ones to dust, dirt, etc., that the babies’ immune systems don’t develop well.

  20. While all of this is fascinating and thought-provoking, I am still trying to understand my son’s circumstances. He was birthed vaginally and exclusively breastfed until 9 months, at which point I finally introduced solids. We did not introduce dairy until almost 15 months. He was diagnosed with reflux at 8 days old, and it was quickly evident that he had food allergies AND intolerances, leading me to be abstinent of dairy starting when he was 4 weeks old, and then abstinent of eggs, soy, wheat, peanuts, and treenuts, all starting when he was 6 weeks old. I nursed until he was 19 months, and not one drop of formula has crossed his lips. He has since been diagnosed with asthma and food and environmental allergies, as well as having multiple illnesses, including a brief hospitalization, in his short 2 1/2 year life.
    I followed all the recommendations in order to reap the benefits of breastfeeding and feel like my body failed both myself and my son. This makes me question the results or generalizations of some of these studies.

    1. Unfortunately, I have heard of similar situations, having been part of an extensive breastfeeding support group. In cases like yours and your baby’s, it is presumed in most cases that if the baby hadn’t been so carefully fed for so many months with mom eliminating allergy-causing fluids and foods, baby might have been a much sicker baby much earlier. Some will dismiss this comment as “rationalization,” but we will never know as testing that theory is impossible. I would encourage such a mom to look on her sincere efforts as still having been best for her baby, and that the allergies and illness are not her fault, but have occurred later than they would have otherwise, and the breast milk still helped the baby in his coping with allergens. I am very thankful that your baby was so conscientiously cared for by you!

  21. A number of studies have linked vitamin D supplements — the vitamin drops recommended for infants — to a significantly increased risk for allergies. This may explain where some of the problems suffered by children come from.

    The “hygiene hypothesis” is very controversial. Its adherents claim that kids raised in super-clean homes have more allergies, which may be true, but they fail to consider the effects all the cleaning agents may have on a child’s health. Microbes are one thing, toxic chemicals are another.

    Kids raised on farms have fewer allergies, but that’s because they eat farm foods, like fresh whole milk, not because they’re exposed to animals or more “dirt.” This has been firmly established by studies from around the world.

  22. Glad to see science catching up with nature. We are animals first. We ignore that fact and create products which make our life easier as compared to other animals, leading to our superiority complex. Let us remember. Nature rules our life. We ignore it to our detriment.

  23. I am currently breast-feeding my fourth child. I have given him formula off and on, much more off than on. There is a SIGNIFICANT difference in his bowl movements when he gets formula. If I were a research scientist, I’d analyze his waste because I think it is an indicator of something going on in his developing gut.

  24. Now I understand why most doctors would say that babies who are breastfed for up to two years of age have a strong immune system. The milk from the mums serve as prebiotics with which probiotics feed on.

  25. @Thonas: “Kids raised on farms have fewer allergies, but that’s because they eat farm foods, like fresh whole milk, not because they’re exposed to animals or more “dirt.” This has been firmly established by studies from around the world.”

    Can you name any of these studies?

    I hate to disappoint you but most farm kids eat just as much processed foods as city kids.

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