#056 The Biology of Breast Milk

Breast Milk: Benefits

I'm very excited to share today's episode with you.

"Hello, friends. I'm very excited to share today's episode with you. As a mother, it covers a topic that is very near and dear to my heart, a topic that has to do with infant and child development."

Omega 3: Dha

Not only that, they appear to enhance the activity of some antibiotics by increasing the membrane permeability of pathogenic bacteria.

"It changes in composition during a single feeding from day to night and throughout the lactation period in response to the growing infant's needs. It's also influenced by circadian rhythms. Breast milk contains several components that transmit circadian signals to help the infant regulate its own sleep-wake cycle, with the nighttime breast milk containing higher levels of melatonin and somnogenic amino acids like tryptophan. Breast milk nucleotides, which are important structural components of DNA and RNA, also show circadian rhythmicity. Some of the nucleotides peak during the day, while others peak at night, suggesting a potential role for these nucleotides as sleep inducers. These data suggest that if an infant is fed expressed breast milk, the milk should be provided at the same time of day that it was expressed to maintain the infant's circadian rhythm. It's important to note that things you eat, drink, supplement, but even more importantly, smoke, can end up in your breast milk. Breast milk is species specific. Human breast milk contains proteins, carbohydrates, fats, vitamins, and minerals to nourish a human infant. One of the biggest differences you'll see between human milk and other types of milk is the protein content. The total protein content in human breast milk is quite a bit lower than milk from other species, one of the reasons human infants grow so slowly compared to, say, a calf. There are roughly 415 different proteins in human breast milk. These proteins provide nutrition, of course, but they also aid in the infant's digestion and supply both antimicrobial and immunological factors that compensate for deficiencies in the infant's immune system, which I'll talk about a little bit later. Breast milk contains a variety of complex carbohydrates, the most abundant of which is lactose, which provides necessary energy for the infant's brain. The second largest concentration of carbohydrates in human breast milk are non-nutritive components called human milk oligosaccharides, or HMOs for short. So let's talk about HMOs, a fascinating part of the story of breast milk. HMOs are complex indigestible sugars. More than 200 different HMOs have been identified in breast milk, making them the third most abundant factor in human breast milk after lactose and fat. These things are super abundant, but here's the surprising part. They aren't there to feed the baby. Instead, HMOs have a very special purpose, which is setting up and feeding and ultimately creating the conditions to select for a strong population of commensal, in other words, healthful bacteria in the infant gut. The origin story of HMOs is similar to those of other examples of mutualism we find throughout the world of biology. Bacteria that benefit us, such as bifidobacteria, get a boost from our own biology as a function of breast milk, whereas bacteria that harm us, pathogenic bacteria, are discouraged from establishing a foothold through a variety of mechanisms. These good bacteria then go on to help set up the immune system through the production of various signaling molecules, such as short-chain fatty acids, which are metabolites produced from the gut bacteria after they metabolize the HMOs. These substances prevent colonization of pathogenic bacteria in the gut. I previously spoke with experts on the gut microbiome, Drs. Justin and Erica Sonnenberg, who spoke a little bit on the topic of HMOs. So babies that are fed formula, their microbiota looks very different than breast milk. And actually what we see is breast milk has a component of it. One of the major components of breast milk is this type of carbohydrate called human milk oligosaccharides or HMOs. And for a long time it was really a mystery why those molecules were there because we knew that humans can't digest human milk oligosaccharides. So why would a mother put so much effort into creating these compounds and putting them in her milk if her baby can't even digest it? We'll come to find out it's actually the gut microbes that are digesting these HMOs. So in breast milk, there's not just food for the baby in the form of lactose and fats, but these HMOs that are food for the baby's growing microbiota, so the mother's feeding the baby and also her baby's growing microbiota. And these HMOs are very specific for human milk and so far have not been able to be replicated in formula. And so that we think is a large reason why the communities are so different. And then, of course, antibiotics. The average American child is on a round of antibiotics every year, and we know that that makes a huge impact on that growing community. So all these things that happen early in life could really set a child on a trajectory potentially for having potentially a very good, healthy, robust microbiota, or potentially one that isn't as good. And so I think as parents, especially of new children, we need to be very mindful of the choices that we make early in a child's life because many of these microbes that we have by the time we're, say, the age of five, many of these microbes will be with us throughout our entire lives. So we really want to get that community started in the best possible way. And nature has come up with a way to get that microbial community started in the best possible way, breast milk. But that's not the end of the story of HMOs. They also serve as decoys to protect the infant from gut infections. In order for bad bacteria to cause infection, they must first target and bind to specific carbohydrates found on the cells that line the gut. However, the overall structure and shape of HMOs mimics that of bacterial targets. The bad bacteria bind to the HMOs instead, preventing them from establishing themselves in the gut. Another interesting quality of HMOs is their capacity to break down biofilms, sticky, slimy communities that bacteria create to protect themselves from antimicrobials and antibiotics. Not only that, they appear to enhance the activity of some antibiotics by increasing the membrane permeability of pathogenic bacteria. So to sum up HMOs, they're the third most abundant factor in human breast milk after lactose and fat, and they play roles in establishing an infant's gut microbial community, a key component of the immune system. They also protect the gut from harmful bacteria by serving as decoys and breaking down the communities in which these harmful bacteria live. Fats are the major source of energy provided in breast milk, supplying roughly half of its total calories. Fats provide energy for growth, aid in the maturation of the infant's gut and central nervous system, and provide protection from pathogens, including group B streptococcus bacteria. Nearly 200 fatty acids have been identified in human breast milk. The structural configuration of these fats, which is not always replicated by many infant formulas, enhances their absorption in the infant's gut. All of these fats are encapsulated in fat globules surrounded by a triple-layered structure called milk fat globule membrane, or MFGM. Components of the MFGM exert bioactive properties that confer many of the antibacterial and anti-inflammatory properties of breast milk. Unfortunately, most infant formulas do not contain MFGM. However, a recent clinical trial found that bovine form of MFGM exerts similar beneficial effects on human infants when included in infant formula. The double-blind randomized controlled trial involved 451 healthy full-term infants who received either regular formula or formula containing MFGM and lactoferrin, an iron-binding protein found in human and cow's milk. At the end of the 18-month long study, the infants who received formula with the MFGM and lactoferrin scored higher on cognitive, language, and motor skills than infants who received ordinary formula. In fact, their scores were similar to those observed in children who were breastfed, suggesting that the addition of MFGM and lactoferrin could narrow the gap in cognitive development commonly observed between formula-fed infants and breastfed infants. The type of fatty acids present in breast milk are strongly influenced by the mother's diet, especially when it comes to the all-important omega-3 fatty acids. For example, when lactating women took a dietary supplement containing 400 milligrams of the marine omega 3 fatty acid DHA, their breast milk contained 123% more DHA than the breast milk of women who took a placebo. DHA is crucial for proper brain development. The infants whose mothers took the DHA supplement also had lower plasma omega-6 to omega-3 ratios. A lower omega-6 to omega-3 fatty acid ratio is more desirable in reducing the risk of many chronic diseases. Smoking cigarettes reduces omega-3 fatty acid uptake, especially DHA, into breast milk. Omega-3 fatty acids play key roles in infant brain development. Intake of DHA in particular is associated with improved mental and psychomotor development. DHA is the most abundant omega-3 fatty acid in a newborn's brain. Maternal intake of omega-3 fatty acids is associated with larger brain volumes in breastfed or mostly breastfed infants. One study involved 92 one-month-old full-term infants who were breastfed exclusively or most of the time. MRI studies reveal that the infants of women who consumed higher quantities of omega-3 fatty acids had greater brain volumes in specific regions of the frontal cortex and corpus callosum, areas of the brain involved in consciousness, communication, memory, attention, and integration of motor, sensory, and cognitive performance between the brain hemispheres. Breast milk also contains vitamins and minerals, but these vary based on a mother's diet and tissue stores. If the mother is undernourished or eats an unhealthy diet, her breast milk may be inadequate to supply sufficient quantities of essential micronutrients to her infant, and supplementation for the mom, infant, or both may be necessary. However, some nutrients are low in breast milk regardless of the mom's diet. For example, vitamin K1, which is essential for normal blood clotting, is very low in breast milk. Consequently, the American Academy of Pediatrics recommends that all newborn infants receive an injection of vitamin K1 to prevent hemorrhaging shortly after birth. Iron is an essential nutrient that plays key roles in infant growth, but breast milk is incredibly low in iron, which might seem counterintuitive. However, microbes require iron for their growth too. To prevent infection, the body restricts microbes' access to iron. Within hours of birth, the infant's serum iron levels drop dramatically. This reduces the infant's risk of developing neonatal sepsis, a generalized life-threatening bacterial infection that commonly occurs within the first days and weeks of life. Infants rely on their iron stores, but by the age of six months, infants can begin to develop iron deficiency anemia. So pediatricians recommend introducing iron-rich complementary foods at that time. Breast milk also contains very little vitamin D, certainly not enough to prevent vitamin D deficiency in exclusively breastfed infants. But recent studies have shown that moms who take a daily high-dose vitamin D supplement of 6,400 IUs a day can increase the vitamin D concentration of their breast milk to a level that provides sufficient vitamin D intake for their infant. And in more bad news about smoking, maternal cigarette smoking impairs the uptake of some nutrients into breast milk. For example, iodine concentrations in the breast milk of women who smoke are roughly half of those of non-smoking women's breast milk. Iodine is critical for brain development and is also important for thyroid function. Rodent studies have found that maternal nicotine exposure impairs thyroid function in offspring and promotes resistance to the hormone leptin, which is associated with obesity. Smokers' breast milk has lower levels of antioxidant vitamins, vitamin C and E, which could drive a pro-oxidant state in the infant. This was demonstrated in a really interesting study where researchers measured levels of ethane, a marker of oxidative stress, in the exhaled air of infants. The breastfed infants of women who smoked exhaled seven times more ethane than the infants of women who did not smoke. Research indicates that exposure to cigarette smoke influences breastfeeding duration. A study of more than 1,200 mother-infant pairs found that women who were exposed to household secondhand smoke were 30% more likely to stop breastfeeding early compared to women who were in non-smoking households. Contrary to the belief that human milk is a sterile solution, breast milk is teeming with hundreds of types of bacteria. They arrive in the mother's milk from a variety of sources, including the mother's skin, retrograde flow from the infant's saliva, aka backwash, and potentially other means. Exposure to this rich bacterial community via breast milk may contribute to the differences observed in gut microbial populations between breastfed and formula-fed infants and provides a rationale for the inclusion of probiotics in infant formulas."

Thyroid Health: Diet

Intake of DHA in particular is associated with improved mental and psychomotor development. DHA is the most abundant omega-3 fatty acid in a newborn's brain.

"It changes in composition during a single feeding from day to night and throughout the lactation period in response to the growing infant's needs. It's also influenced by circadian rhythms. Breast milk contains several components that transmit circadian signals to help the infant regulate its own sleep-wake cycle, with the nighttime breast milk containing higher levels of melatonin and somnogenic amino acids like tryptophan. Breast milk nucleotides, which are important structural components of DNA and RNA, also show circadian rhythmicity. Some of the nucleotides peak during the day, while others peak at night, suggesting a potential role for these nucleotides as sleep inducers. These data suggest that if an infant is fed expressed breast milk, the milk should be provided at the same time of day that it was expressed to maintain the infant's circadian rhythm. It's important to note that things you eat, drink, supplement, but even more importantly, smoke, can end up in your breast milk. Breast milk is species specific. Human breast milk contains proteins, carbohydrates, fats, vitamins, and minerals to nourish a human infant. One of the biggest differences you'll see between human milk and other types of milk is the protein content. The total protein content in human breast milk is quite a bit lower than milk from other species, one of the reasons human infants grow so slowly compared to, say, a calf. There are roughly 415 different proteins in human breast milk. These proteins provide nutrition, of course, but they also aid in the infant's digestion and supply both antimicrobial and immunological factors that compensate for deficiencies in the infant's immune system, which I'll talk about a little bit later. Breast milk contains a variety of complex carbohydrates, the most abundant of which is lactose, which provides necessary energy for the infant's brain. The second largest concentration of carbohydrates in human breast milk are non-nutritive components called human milk oligosaccharides, or HMOs for short. So let's talk about HMOs, a fascinating part of the story of breast milk. HMOs are complex indigestible sugars. More than 200 different HMOs have been identified in breast milk, making them the third most abundant factor in human breast milk after lactose and fat. These things are super abundant, but here's the surprising part. They aren't there to feed the baby. Instead, HMOs have a very special purpose, which is setting up and feeding and ultimately creating the conditions to select for a strong population of commensal, in other words, healthful bacteria in the infant gut. The origin story of HMOs is similar to those of other examples of mutualism we find throughout the world of biology. Bacteria that benefit us, such as bifidobacteria, get a boost from our own biology as a function of breast milk, whereas bacteria that harm us, pathogenic bacteria, are discouraged from establishing a foothold through a variety of mechanisms. These good bacteria then go on to help set up the immune system through the production of various signaling molecules, such as short-chain fatty acids, which are metabolites produced from the gut bacteria after they metabolize the HMOs. These substances prevent colonization of pathogenic bacteria in the gut. I previously spoke with experts on the gut microbiome, Drs. Justin and Erica Sonnenberg, who spoke a little bit on the topic of HMOs. So babies that are fed formula, their microbiota looks very different than breast milk. And actually what we see is breast milk has a component of it. One of the major components of breast milk is this type of carbohydrate called human milk oligosaccharides or HMOs. And for a long time it was really a mystery why those molecules were there because we knew that humans can't digest human milk oligosaccharides. So why would a mother put so much effort into creating these compounds and putting them in her milk if her baby can't even digest it? We'll come to find out it's actually the gut microbes that are digesting these HMOs. So in breast milk, there's not just food for the baby in the form of lactose and fats, but these HMOs that are food for the baby's growing microbiota, so the mother's feeding the baby and also her baby's growing microbiota. And these HMOs are very specific for human milk and so far have not been able to be replicated in formula. And so that we think is a large reason why the communities are so different. And then, of course, antibiotics. The average American child is on a round of antibiotics every year, and we know that that makes a huge impact on that growing community. So all these things that happen early in life could really set a child on a trajectory potentially for having potentially a very good, healthy, robust microbiota, or potentially one that isn't as good. And so I think as parents, especially of new children, we need to be very mindful of the choices that we make early in a child's life because many of these microbes that we have by the time we're, say, the age of five, many of these microbes will be with us throughout our entire lives. So we really want to get that community started in the best possible way. And nature has come up with a way to get that microbial community started in the best possible way, breast milk. But that's not the end of the story of HMOs. They also serve as decoys to protect the infant from gut infections. In order for bad bacteria to cause infection, they must first target and bind to specific carbohydrates found on the cells that line the gut. However, the overall structure and shape of HMOs mimics that of bacterial targets. The bad bacteria bind to the HMOs instead, preventing them from establishing themselves in the gut. Another interesting quality of HMOs is their capacity to break down biofilms, sticky, slimy communities that bacteria create to protect themselves from antimicrobials and antibiotics. Not only that, they appear to enhance the activity of some antibiotics by increasing the membrane permeability of pathogenic bacteria. So to sum up HMOs, they're the third most abundant factor in human breast milk after lactose and fat, and they play roles in establishing an infant's gut microbial community, a key component of the immune system. They also protect the gut from harmful bacteria by serving as decoys and breaking down the communities in which these harmful bacteria live. Fats are the major source of energy provided in breast milk, supplying roughly half of its total calories. Fats provide energy for growth, aid in the maturation of the infant's gut and central nervous system, and provide protection from pathogens, including group B streptococcus bacteria. Nearly 200 fatty acids have been identified in human breast milk. The structural configuration of these fats, which is not always replicated by many infant formulas, enhances their absorption in the infant's gut. All of these fats are encapsulated in fat globules surrounded by a triple-layered structure called milk fat globule membrane, or MFGM. Components of the MFGM exert bioactive properties that confer many of the antibacterial and anti-inflammatory properties of breast milk. Unfortunately, most infant formulas do not contain MFGM. However, a recent clinical trial found that bovine form of MFGM exerts similar beneficial effects on human infants when included in infant formula. The double-blind randomized controlled trial involved 451 healthy full-term infants who received either regular formula or formula containing MFGM and lactoferrin, an iron-binding protein found in human and cow's milk. At the end of the 18-month long study, the infants who received formula with the MFGM and lactoferrin scored higher on cognitive, language, and motor skills than infants who received ordinary formula. In fact, their scores were similar to those observed in children who were breastfed, suggesting that the addition of MFGM and lactoferrin could narrow the gap in cognitive development commonly observed between formula-fed infants and breastfed infants. The type of fatty acids present in breast milk are strongly influenced by the mother's diet, especially when it comes to the all-important omega-3 fatty acids. For example, when lactating women took a dietary supplement containing 400 milligrams of the marine omega 3 fatty acid DHA, their breast milk contained 123% more DHA than the breast milk of women who took a placebo. DHA is crucial for proper brain development. The infants whose mothers took the DHA supplement also had lower plasma omega-6 to omega-3 ratios. A lower omega-6 to omega-3 fatty acid ratio is more desirable in reducing the risk of many chronic diseases. Smoking cigarettes reduces omega-3 fatty acid uptake, especially DHA, into breast milk. Omega-3 fatty acids play key roles in infant brain development. Intake of DHA in particular is associated with improved mental and psychomotor development. DHA is the most abundant omega-3 fatty acid in a newborn's brain. Maternal intake of omega-3 fatty acids is associated with larger brain volumes in breastfed or mostly breastfed infants. One study involved 92 one-month-old full-term infants who were breastfed exclusively or most of the time. MRI studies reveal that the infants of women who consumed higher quantities of omega-3 fatty acids had greater brain volumes in specific regions of the frontal cortex and corpus callosum, areas of the brain involved in consciousness, communication, memory, attention, and integration of motor, sensory, and cognitive performance between the brain hemispheres. Breast milk also contains vitamins and minerals, but these vary based on a mother's diet and tissue stores. If the mother is undernourished or eats an unhealthy diet, her breast milk may be inadequate to supply sufficient quantities of essential micronutrients to her infant, and supplementation for the mom, infant, or both may be necessary. However, some nutrients are low in breast milk regardless of the mom's diet. For example, vitamin K1, which is essential for normal blood clotting, is very low in breast milk. Consequently, the American Academy of Pediatrics recommends that all newborn infants receive an injection of vitamin K1 to prevent hemorrhaging shortly after birth. Iron is an essential nutrient that plays key roles in infant growth, but breast milk is incredibly low in iron, which might seem counterintuitive. However, microbes require iron for their growth too. To prevent infection, the body restricts microbes' access to iron. Within hours of birth, the infant's serum iron levels drop dramatically. This reduces the infant's risk of developing neonatal sepsis, a generalized life-threatening bacterial infection that commonly occurs within the first days and weeks of life. Infants rely on their iron stores, but by the age of six months, infants can begin to develop iron deficiency anemia. So pediatricians recommend introducing iron-rich complementary foods at that time. Breast milk also contains very little vitamin D, certainly not enough to prevent vitamin D deficiency in exclusively breastfed infants. But recent studies have shown that moms who take a daily high-dose vitamin D supplement of 6,400 IUs a day can increase the vitamin D concentration of their breast milk to a level that provides sufficient vitamin D intake for their infant. And in more bad news about smoking, maternal cigarette smoking impairs the uptake of some nutrients into breast milk. For example, iodine concentrations in the breast milk of women who smoke are roughly half of those of non-smoking women's breast milk. Iodine is critical for brain development and is also important for thyroid function. Rodent studies have found that maternal nicotine exposure impairs thyroid function in offspring and promotes resistance to the hormone leptin, which is associated with obesity. Smokers' breast milk has lower levels of antioxidant vitamins, vitamin C and E, which could drive a pro-oxidant state in the infant. This was demonstrated in a really interesting study where researchers measured levels of ethane, a marker of oxidative stress, in the exhaled air of infants. The breastfed infants of women who smoked exhaled seven times more ethane than the infants of women who did not smoke. Research indicates that exposure to cigarette smoke influences breastfeeding duration. A study of more than 1,200 mother-infant pairs found that women who were exposed to household secondhand smoke were 30% more likely to stop breastfeeding early compared to women who were in non-smoking households. Contrary to the belief that human milk is a sterile solution, breast milk is teeming with hundreds of types of bacteria. They arrive in the mother's milk from a variety of sources, including the mother's skin, retrograde flow from the infant's saliva, aka backwash, and potentially other means. Exposure to this rich bacterial community via breast milk may contribute to the differences observed in gut microbial populations between breastfed and formula-fed infants and provides a rationale for the inclusion of probiotics in infant formulas."

Caffeine: Sleep

Another amazing component of breast milk is stem cells.

"Another amazing component of breast milk is stem cells. Human breast milk contains stem cells from the mother called mammary stem cells that preclinical research indicates may help establish organs like the liver, kidneys, pancreas, and brain."