Written by: Lauren Milligan Newmark, Ph.D. | Issue # 66 | 2017
- A new study reports that 30% of the bacteria in infant’s guts are associated with bacteria in breast milk.
- Breastfeeding frequency was positively associated with diversity of gut bacterial strains.
- Beneficial bacteria provided by breast milk may act as seeds in the infant gut, selecting for future generations of bacteria that regulate metabolism and enhance immune function.
- Having a diverse community of beneficial bacteria in the gastrointestinal tract is associated with positive health outcomes from infancy through adulthood.
Twenty years ago, breast milk was believed to be sterile—any bacteria present were assumed to originate from the infant’s mouth or the mother’s skin . Fast-forward to 2017, and bacteria are not viewed as contaminants but as ubiquitous and possibly important ingredients of breast milk. Recent research suggests a link between the infant’s gut bacterial community, or microbiome, and the adult microbiome; starting out with the right mix of beneficial bacteria in the gut influences health throughout the lifespan [2–4]. The infant’s gut is initially colonized by bacteria that may come from different sources, such as breast milk, or worse, such as a hospital environment. Special carbohydrates in breast milk, such as free oligosaccharides or glycans attached to proteins, then selectively nurture the good bacteria.
What can a parent do to make sure their offspring’s gastrointestinal tract has the most beneficial strains of bacteria? The results of a new study  out of UCLA and Children’s Hospital Los Angeles demonstrate that breast milk-derived microbes make up almost one-third of all beneficial bacteria in the infant’s gut. Far from contaminating, breast milk bacteria may be instrumental in getting the gut off to a good start.
The Good Guys
Bacteria have been given a bum rap. Ask someone about bacteria in the gut and they are likely to think of infectious agents like Escherichia coli, C-diff (Clostridium difficile), and cholera. However, the overwhelming majority of bacteria living in the human gut (estimated to be in the trillions!) are commensal, meaning they have no negative impact on their host, or mutualistic, meaning they provide a benefit to the host [3–5]. In fact, these bacteria are considered so essential to metabolism and immune function that they are often referred to as “the forgotten organ” .
Take food digestion, for example. The stomach and the intestines get much of the credit, but beneficial gut bacteria help break down otherwise indigestible plant starches and fibers and enhance the absorption of nutrients [4–6]. In doing so, they also create useful metabolic byproducts, such as short-chain fatty acids that are important sources of energy for the host and also feed other beneficial bacteria [4,5].
The spleen, thymus, and lymph nodes are important immune organs but are also highly reliant on gut microbes to train the immune cells exactly what “bad” bacteria look like [4–6]. Those immune organs can also thank beneficial bacteria for making their jobs easier. By forming a protective barrier along the surface of the intestines, beneficial bacterial strains keep pathogens from ever reaching host tissues and stimulating an immune response.
But the intestinal microbiome does more than help out the host’s immune system—it is actively involved in regulating that system. As a result, there is a strong link between the strains of bacteria that make up an individual’s microbiome and their health . For example, some bacterial strains enhance the anti-inflammatory response of lymphocytes. Animal studies demonstrate that when these strains are not well represented in the microbiome, the resulting pro-inflammatory bias can trigger diseases such as Chron’s and inflammatory bowel disease [3,5]. The make-up of the gut microbiome has also been linked to obesity and the metabolic syndrome. The very same bacteria that help to extract nutrients and energy from foods have been linked to higher body mass index, obesity, and altered metabolism—having some of these bacteria is essential, but having too many is associated with negative health outcomes [2,5]. Thus, although there is not a one-size-fits-all for healthy guts, researchers have converged on the concept of diversity and balance of bacterial strains when trying to describe the optimal gut microbiome [2–6].
If an abnormal gut microbiome is a gut with too many of one strain of bacteria and too few of another, then what can be done to make sure not to tip the balance? Several lines of evidence demonstrate that building a balanced and diverse gut microbiome starts early…really early .
Baby’s First Microbes
Parents can recall all of baby’s “firsts”—first steps, first word, and the first day of school are carefully recorded and photographed. But very few parents probably even consider the sources of their baby’s first microbial exposure despite the overwhelming evidence suggesting the sources of exposure can influence health in infancy and throughout the lifespan [1-3].
Until recently, it was believed that infants start their life with a clean slate, born free of any bacterial colonization. However, evidence for bacterial strains in the meconium (stool produced from materials consumed while the infant is in utero) argues against this “sterile infant” perspective . The placenta may have its very own microbiome and could potentially represent the first source of maternal-offspring microbial transfer [7,8]. The second exchange occurs during childbirth when the newborn is exposed to bacteria from the vagina, and potentially even maternal fecal bacteria. Both exchanges are viewed as adaptations, where mothers provide infants with a “microbial inoculum”  before exposure to any other environmental microbes. Disrupting these opportunities, either through antibiotic use during pregnancy or birth via C-section, can increase the risks of developing celiac disease, type 1 diabetes, asthma, and obesity [6–8].
And then comes breast milk. Milk does not simply provide more of the same maternal microbes as previous sources; bacterial communities provided by breast milk are unique from those transferred via placenta or through vaginal birth. Bacteria genera commonly isolated from breast milk samples include Bifidobacterium, Lactobacillus, Clostridium, Ralstonia, Staphylococcus, and Streptococcus [1,4,7]. The last two in that list may sound familiar, and not in a good way; both genera include strains of pathogens known to cause disease in humans. It seems surprising, then, that these are usually among the dominant genera in breast milk. However, not all species in these genera are infectious agents. For example, some strains may provide benefits to the hosts by preventing colonization of the gut from their more lethal cousins . Another possibility is that disease-causing strains are passed from mother to offspring, but the presence of other beneficial bacteria or other antimicrobial agents in milk negates their actions.
These hypotheses deserve more investigation and studies on milk bacteria should employ techniques that allow for detection at the level of the species, rather than just the genera, because breastfeeding is considered one of the most critical postpartum factors influencing the programming of metabolism and the immune system [2,5]. As was true of prenatal disruptions in the transfer of microbes from mother to offspring, the use of formula in place of breast milk has been linked to increased risks of poor health outcomes, including autoimmune diseases, inflammatory diseases of the gastrointestinal tract, and metabolic syndrome .
The reason the effects of antibiotic use, C-section, and formula (each of which is a novel, cultural development) are often realized long after the colonizing events is because the earliest microbes select for their predecessors . Just as you can send off your DNA-laden spit and get a report detailing your ancestral origins, researchers can analyze fecal bacteria and determine the first microbes to seed your gut [2,6]. For this reason, Pannaraj and colleagues  argue that the earliest stages of life, including the time spent in utero and during birth, are a critical window for building a healthy gut microbiome.
Planting The Seeds
Despite such an important role in short- and long-term health outcomes, it may be surprising to learn that researchers are still trying to quantify how much of the beneficial bacteria in the gut is provided by breast milk and how much comes from other sources, such as maternal skin and the infant’s environment. In the largest study to date to tackle this question, Pannaraj and colleagues  analyzed the bacterial composition of breast milk, maternal areolar skin, and infant stool in 107 mother-infant pairs. Importantly, not all 107 infants were exclusively breastfeeding when the milk and stool samples were collected. As such, the researchers were able to explore the influence of nursing duration, nursing frequency, and the introduction of solid foods on the composition of the infant microbiome.
The bacterial communities in the milk and the mother’s skin were distinct, and each was found to make a different contribution to the infant’s gut microbiome. In the first 30 days of lactation, in infants that were primarily breastfed (defined by the research team as receiving at least 75% or more of their milk from breast milk) nearly 28% of their gut bacteria matched those from mother’s milk and just over 10% of bacteria matched those from areolar skin .
As all the infants aged, the contribution from milk and areolar skin to their gut microbiome decreased. However, the way in which the infants’ gut microbiomes changed over time was associated with the percentage of daily breast milk intake in a dose-dependent manner . Exclusively breast-fed infants had bacterial communities that were distinct from those that received both milk and formula, indicating that even small amounts of formula have the potential to shift the microbial communities in the gut away from the breastfeeding pattern . Interestingly, these differences seemed to persist even after the introduction of solid foods, which represent a source of novel microbes. Pannaraj and colleagues found that that dramatic shift in bacterial communities that usually occurs when food-derived bacteria are introduced was suppressed in infants that continued to receive at least 75% of milk from the breast after the introduction of solid foods . An early maturation (that is, the development of an adult-like microbiome) has been associated with several negative health outcomes, including asthma and obesity .
Taken together, the results of this study suggest that breast milk makes its largest contribution to the infant gut microbiome during the first month of life but continues to positively influence the diversity of microbes throughout lactation. This supports the current World Health Organization’s recommendation to breastfeed exclusively for the first six months of life and to continue breastfeeding through at least the first year.
The researchers accounted for the sources for 40% of the infant’s beneficial gut bacteria, but where does the other 60% come from? Unfortunately, this study did not investigate alternative sources but acknowledges that exposure to vaginal and fecal bacteria during childbirth and the environment are major contributors. Additionally, other researchers have suggested the location of birth (i.e., at home vs. a hospital) may provide another important source (or lack thereof) of microbial exposure .
Even without quantifying the individual contribution of mode of delivery and early infant environment, it seems reasonable to assume that evolutionary novel events such as C-sections and hospital births may be associated with suboptimal microbial development . However, because these events may not be avoidable (e.g., C-section due to maternal pre-eclampsia or infant distress), it would be worthwhile to investigate how much breastfeeding may restore the balance in the microbiome.
Finally, perhaps the largest question that remains unanswered from this and other studies of its kind is the source of the breast milk bacteria. Recall that the bacterial strains from the milk and the maternal skin were distinct communities ; this indicates that the skin of the mother’s breast is not the source for all breast milk bacteria. But if it is not from the skin, then where is it coming from? One possible hypothesis is that there is a connection between the maternal gut microbiome and the mammary gland . Maternal immune cells may be responsible for carrying bacterial strains on a special intracellular route referred to as the entero-mammary pathway [1,4]. This proposition is not without controversy, but it is supported through several lines of evidence. Several studies in mouse models support the ability of dendritic cells to carry bacteria to locations in the body outside the gut, in a process known as translocation . Moreover, human and mice mothers fed specific strains of probiotics (not commonly found in milk) produced milk containing that specific probiotic . Finally, Pannaraj et al.  found that infant’s stool microbiome was closer to that of its own mother’s microbiome compared to a random mother from the study. That is, although there are common bacteria genera passed on in milk from all mothers, microbial profiles are unique to mother-infant dyads.
It is important to note, however, that infant gut microbiomes are distinct from their mother’s. Thus, cells are not just bringing any microbes from the mother’s gut to the mammary glands; they have instructions to only bring specific strains. Another possible hypothesis, which would also be supported by the observations of shared strains of mother and baby, is a fecal-oral route of contamination. For most of human history, there hasn’t been modern plumbing and even with modern plumbing, most babies are still born through an opening that is very near the fecal canal.
Despite these issues, studies like that from Pannaraj and colleagues  highlight the importance of breast milk in establishing a healthy gut. We might not know where the bacteria come from, but it is becoming clear that they have the potential to improve health outcomes throughout the lifespan.
1. Rodriguez J.M. 2014. The origin of human milk bacteria: is there a bacterial entero-mammary pathway during late pregnancy and lactation? Adv Nutr. 5: 779–784.
2. Pannaraj P.S., Li F., Cerini C., Bender J.M., Yang S., Rollie A., Adisetiyo H., Zabih S., Lincez P.J., Bittinger K., Bailey A., Bushman F.D., Sleasman J.W., Aldrovandi G.M. 2017. Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatr. doi: 10.1001/jamapediatrics.2017.0378
3. Hooper L.V., Littman D.R., Macpherson A.J. 2012. Interactions between the microbiota and the immune system. Science 336: 1268–1273.
4. Martin M.A., Sela D.A. 2013. Infant gut microbiota: developmental influences and health outcomes. In Building babies, pp. 233–256. Springer: New York.
5. Quigley E.M.M. 2013. Gut bacteria in health and disease. Gastroenterology and Hepatology 9: 560–566.
6. Cabrera-Rubio R., Collado M.C., Laitinen K., Salminen S., Isolauri E., Mira A. 2012. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr. 96: 544–551.
7. Mueller N.T., Bakacs E., Combellick J., Grigoryan Z., Dominguez-Bello M.G. 2015. The infant microbiome development: mom matters. Trends Mol Med. 21: 109–117.
8. Aagaard K., Ma J., Antony K.M., Ganu R., Petrosino J., Versalovic J. 2014. The placenta harbors a unique microbiome. Sci Transl Med. 6:237ra65.