Nutrients acquired by the mother through ingested food fuel development in the womb (in utero). The placenta mediates the transfer of nutrients, as well as oxygen and waste products, between the maternal blood flow and the fetus.1 As a result, nutrient acquisition and waste elimination in utero occur independently of the gastrointestinal (GI) tract, relying on fetal blood circulation instead.1 This fundamentally changes at birth, when the newborn’s GI tract is exposed to food for the first time.2 Another major change at birth is the transition from the relatively sterile environment of the womb to a bacteria-filled world. Rapid microbial colonization of the body occurs at birth, with the GI tract harbouring a greater density of bacteria and other microbes than any other site of the body.2 In recent years, there has been growing interest around this initial colonization, the changes that occur within these bacterial populations within the first years of life, and their implications on later health.
Factors influencing newborn bacterial populations
Altered intestinal bacterial populations in early life have been associated with increased susceptibility for the later development of allergies, asthma, obesity, and other inflammatory diseases.3,4,5,6 For instance, researchers have associated low colonization rates of infants with two groups of bacteria well known for their probiotic effects in both adults and infants (bifidobacteria and lactobacilli) with later development of allergies.7 Several factors can influence intestinal bacterial populations, the most immediate one at birth being how the baby was born.4 Vaginal and fecal bacteria from the mother first colonize babies born vaginally, including Lactobacillus and Bifidobacterium.4 Bacteria from the hospital environment and skin, on the other hand, are the first colonizers in caesarian born babies. These include members of the Staphylococcus and Acinetobacter groups, small numbers of which are also found in the adult GI tract.3,4 Geographic location, genetics, level of gestational development at birth, and exposure to antibiotics also likely influence the makeup of the bacterial population at this time.3 Interestingly, one of the most significant factors shaping intestinal bacterial populations at this time is the newborn’s food source: breast milk or formula.3,6
Breast milk: composition and benefits
Breast milk is a complex biological fluid that has evolved as the exclusive nutrient source for newborn development.8 In addition to providing adequate proteins, fats, and carbohydrates to fuel development, breast milk contains many antimicrobial factors, growth factors and other hormones, beneficial microbes, and immune-protective molecules.9 Breast milk also contains a large quantity of carbohydrates that cannot be digested by the newborn, referred to as milk oligosaccharides.9 However, some intestinal bacteria, such as Bifidobacterium and Lactobacillus, can digest milk oligosaccharides.9 This is hypothesized to be one of the ways in which breast milk can shape bacterial populations. Given these properties, it is not surprising that breast-fed infants have lower rates of infection and diarrhea than those fed by formula, and might be at decreased risk for the later development of allergies, metabolic diseases, asthma, and other inflammatory diseases.6,10
Breastfeeding also decreases the risk of developing necrotizing enterocolitis in babies born prematurely.11 Necrotizing enterocolitis is a devastating disease that affects 7-10% of infants born before 32 weeks of gestation and is characterized by widespread intestinal inflammation and death of small intestinal tissue sections.
As breast milk isn’t always available or an option for some mothers and their newborns, baby formula serves as a necessary alternative. Given the many protective qualities of breast milk, it is essential that formula mimic breast milk as closely as possible. Interestingly, human donor milk that is pasteurized does not seem to offer the same level of protection as fresh breast milk against necrotizing enterocolitis.11 This lack of protection with donor milk is likely because of the need for pasteurization and freezing due to the potential transfer of pathogens to the premature infant. As these processes can alter components of the donor milk,12 an analysis of the differences between donor and breast milk offers insights into what can be added into formula for it to more closely mimic breast milk. The fat portion of breast milk, which provides around half of its energy (45-55%), is one component that the pasteurization process disrupts.12 Further, current formulas derive their fat component from vegetable sources, which have a very different size and composition than breast milk fat.13
Milk Fat Globule Membrane (MFGM)
The fat portion of breast milk, and other mammalian milk such as cow’s milk, has a very unique structure.12,13 It consists of large droplets, mainly composed of triglycerides (fat molecules), surrounded by a rare triple membrane structure, referred to as the MFGM.13 The MFGM is formed as cells in the lactating mammary gland secrete the triglyceride droplet into the milk ducts, taking the proteins and other signalling molecules embedded in the cell membrane with it.13 The proteins within the MFGM account for 1-4% of the total proteins in the milk, some of which have antimicrobial properties and others act as growth factors.13,14 In addition, some MFGM proteins are heavily glycosylated, a process through which carbohydrates are added to their structure.14 These carbohydrates may serve as a food source for probiotic strains of bacteria in the intestine, similar to milk oligosaccharides. Since pasteurization and homogenization disrupt the fat component of mammalian milk, products sold at grocery stores do not contain a MFGM fat portion.13 However, recent progress in extraction technologies of MFGM from unpasteurized cow’s milk has made its upscaling a possibility,13 and has allowed researchers to examine the effects of its addition to formula in animal models and in clinical studies.
Clinical studies examining the effects of MFGM supplemented formula in infants have revealed that the formula is safe and well tolerated, has positive effects on neurodevelopment, and decreases incidence of a painful ear infection that occurs in infants (acute otitis media).15,16,17 In animal studies, MFGM supplementation in adult models is reported to be protective against the development of sepsis, gastric ulcers, and colon cancer.18,19
Since most of the existing analysis for the effects of MFGM in newborn infants and animals has focused on brain development, our group sought to examine its effects in intestinal development and protection in a newborn rodent model.20 Interestingly, supplementation of MFGM to formula resulted in similar development in the small and large intestine as pups fed mother’s milk in terms of growth of intestinal tissue, numbers of mucus producing cells, antimicrobial producing cells, and proteins sealing the intestinal barrier. In comparison, pups fed formula lacking MFGM were delayed in their intestinal development of these same factors. In addition, pups fed MFGM formula harboured intestinal bacteria that had greater similarity to mother’s milk fed pups, with a population of lactobacilli present that was absent in the pups fed formula lacking MFGM. Finally, the addition of MFGM protected the formula fed pups from intestinal damage by bacterial toxins. This study suggests that the addition of MFGM to formula has positive effects during intestinal development and is protective against harmful toxins. These findings are especially of interest with regards to vulnerable populations, such as infants born prematurely that may have an increased risk of developing potentially devastating intestinal conditions such as necrotizing enterocolitis.
Where do we go from here?
Research in both clinical settings and with animal models, as described above, has indicated positive results for the addition of MFGM to formula. It is not surprising that the United States has recently approved formulas containing MFGM for sale, though Canada has yet to approve these products. This provides a great opportunity to examine the effects of MFGM on long-term health and in determining if we have, in fact, taken formula one step closer to mimicking human breast milk.