The Joy of Why - What Does Milk Do for Babies?

Episode Date: April 25, 2024

Milk is more than just a food for babies. Breast milk has evolved to deliver thousands of diverse molecules including growth factors, hormones and antibodies, as well as microbes. Elizabeth Johnson, a molecular nutritionist at Cornell University, studies the effects of infants’ diet on the gut microbiome. These studies could hold clues to hard questions in public health for children and adults alike. In this episode of “The Joy of Why” podcast, co-host Steven Strogatz interviews Johnson about the microbial components that make breast milk one of the most wondrous biofluids found in nature. You can read the transcript for this episode and see the image of the micrograph Johnson references on our website.

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Milk is such a homey, familiar substance that it might seem too ordinary to hold any mysteries. Yet in reality, milk and the act of nursing are extraordinary biological innovations that researchers are still trying to understand. It's well known that breast milk can help ensure the health of nursing infants, but those benefits aren't simply a result of milk's nutritional content. Along with being a source of nourishment, milk also provides

protection against germs, stimulates infant development, and allows mom and baby to have all sorts of chemical conversations. Breast milk contains thousands of diverse molecules, including growth factors, hormones, antibodies, and microbes. All of these work in concert to provide human babies with what they need to grow and develop normally. But how exactly? I'm Steve Strogatz, and this is The Joy of Why, a podcast from Quantum Magazine, where my co-host Jana Levin and I take turns exploring some of the biggest unanswered questions in math and science today. In this episode, we'll talk with molecular biologist Elizabeth Johnson about the mysteries of milk and how we've evolved to be so dependent on this

all-powerful, all-natural substance. Liz is an assistant professor of molecular nutrition at Cornell University in the Division of Nutritional Sciences and a Howard Hughes Medical Institute Freeman Hrabowski scholar. She specializes in genomic and metabolomic approaches to studying the effects of nutrition on the gut microbiome, with particular interest in infant nutrition and the infant gut microbiome. Liz, welcome to The Joy of Why. Thank you for having me, Steve. My pleasure. I'm very happy to see you. I don't think it's exactly relevant, but I can't resist saying that we're almost next-door neighbors. There's one house in between us. Liz is my very

good friend as well as esteemed colleague. Yeah, no, I think that's one house in between us. Liz is my very good friend as well as esteemed colleague. Yeah, no, I think that's a good point to make. All right. So now that disclosure is out of the way, let me just confess, I don't know the first thing about milk as a scientific subject. I was shocked as I was doing a little research for this show about just how many puzzles there are still remaining. As a little kid, when I would come home after school, I'd have milk and cookies. Maybe I'd have peanut butter and jelly. So from that way of thinking about it, milk is just another kind of food.

Let's talk about it first as food. What are the fundamental nutritional components of milk? The context that you're talking about was the same way that I used to think about milk. Not that it was food for babies, but that it was just food, something that tasted pretty good. As you get older and you realize how specialized milks can be, especially when you may have an infant that needs milk and you start thinking about human milk, that's when you realize there's more to milk than I really thought about when I was having those cookies and milk as a kid. What it really is, it's composed of things that are needed for the

nutrition of babies for a short period of time. And it's a very characteristic trait of all mammals which use milk to feed their babies. And so when you think about what's really in it, there are sugars, so carbohydrates, there are fats, there are proteins, there are minerals. And in human milk and many other milks, there are other factors such as immune factors and other cells and nucleic acids and things like that, that are also not just for growth, but also for the development during that period of time. So when you pick up a cold glass of milk, it was really designed to do a lot more than it's doing right now. So you have opened the door now to this larger role that milk can play, that it's much more than a food. It's everything you ever read about in your biology

textbook. Is that right? Enzymes, hormones, antibodies, stem cells, microbes, things that aren't even exactly human? Yeah, exactly. And it is a great source of nutrition. You're thinking about something that's going to allow for the most rapid growth and development of a human outside of the womb, right? But then you think there's also this really great opportunity here for communication, right? A lot of the information that right? But then you think there's also this really great opportunity here for communication, right? A lot of the information that's there can be transferred through the act of chest feeding. And this is a very important thing that we forget about when we think about it as just like the consumer product or just something that's for energy needs.

By information here, can you give us an example of what kind of information? Is it two-way communication? Are they each talking to each other? Yeah, there's some evidence that it can be two ways. There can be saliva information and baby saliva. You can imagine if there was a virus or other particles that are there that might be interacting with the mammary or at the breast. And then also whatever gets put into milk through the milk ducts.

So lactation is the production of milk and then the ejection of milk. So whatever is ejected in there is something that potentially the infant is going to consume and then the cells and the organs of the infant can then process that. And some of that we can call information. and the organs of the infant can then process that. And some of that we can call information. They may be small molecules or other chemical signals that are really important for growth and development during that period of time.

We're still trying to understand what those are because we want to understand, are they necessary for health? What happens when you don't see some of these signals? And how do we think about feeding babies in the most optimal way with this type of information? Let's start exploring some of that. For example, let's just talk about like variation from person to person. It stands to reason that the ingredients wouldn't be exactly the same from one person to another. Maybe the fat content would

change or the antibodies that get transferred are different. But does milk vary even more than that from person to person, say over the course of time, over the course of breastfeeding? Oh, most definitely. The most famous example of this is colostrum. This is a first milk, which is a very high protein dense milk.

It looks kind of gold. It's like liquid gold and it comes in very small amounts. And that's in the first moments of life, the nutrition that baby is getting. But then over the next five to seven days, there's this maturation of milk where you go from this very protein dense substance to a watery, more sugary kind of milk that might be the milk that's going

to sustain growth across the next few months. And so there's this biological process that happens that is characteristic of lactation. But to your point, I don't think we even have a grasp on how much milk can vary between individuals on a day to day. And that's something that my lab is trying to do. Like if you just look at milk every single day of lactation, is it very similar or is it changing to many of the life events that may happen during the first six months of life? There have been some really amazing studies that show that diet has an influence. So the particular things that get into milk can be dependent on that. And you can imagine that there are some regional specificities to that, that would allow for milks

of certain populations to look more similar than other populations. You'll still see variation, not just across individuals, but there is individual temporal variation throughout the day. There is also time of the feed. So there is a foremilk and there's a hindmilk. I don't know those terms, foremilk and hindmilk. Yeah. When a baby latches on, that feed may last anywhere from five to 30 minutes or even longer. And throughout the course of that feed, the macronutrient composition of milk can change. The milk in the beginning of the feed is going to have a different macronutrient composition, and that's the foremilk than the hind milk, which comes at the end of the feed. I always call it nature's most interesting biofluid

because there are so many complications to how we understand it, but if we treat those in the right way, we actually learn a lot of information. Oh, that's great. I can't think of what other biofluid could rival it. Blood is complicated, I suppose, but milk may be the champ. Yeah, I like to put a word in for milk. What is fascinating about milk in terms of understanding human health is that everything you need to nourish a human baby is in this one substance that we can quantify and we can look at and we don't have to guess. The answers are there and we then have the opportunity to decode some of those answers as we get better

at analyzing milk and understanding the right questions to ask. But it's very different than how maybe you and I feed ourselves, where we're making our own decisions. And we might be making good decisions and bad decisions. And those might have good or bad consequences on our health. But when we're thinking during infancy, and we're thinking about human milk, the good is there and we just need to understand why. So earlier you mentioned about the diet of the caregiver. And actually, while I'm on this, I say caregiver here to include mothers, but also let's keep in mind other people, wet nurses, breast milk, donors, trans people, anyone who might be providing milk. I usually say caregivers or a lactating parent.

When you look at family units, there's a lot going on. So it's really important to be very inclusive of everything that's going on during this period of time when we think about feeding babies and all the many people who feed babies. On this question of diet, how does the diet of the caregiver affect the composition of the milk that they produce? I think we're still trying to understand exactly how that works. So you can think of this on a macro scale. In my lab, we focus on the fat fraction of milk. In human milk, it's a fascinating fraction of milk to study because it's really responsible for all the calories. It's also responsible for a lot of small molecules and chemical signals that have not been quantified that are extremely important. And so when we think about the different types of fats that are in milk, they can come from many different places.

They can either be synthesized in the mammary, they can come from circulation, but the ones that are coming from circulation can be directly related to what the particular mother or lactating parent is actually consuming, because that can change the profile of what structures of fats are in milk. Maybe some of the most famous would be, let's say, if you are eating a lot of fatty fish, polyunsaturated fatty acids, omega-3 fatty acids, and things like that, you can have different profiles of those in milk based off of the consumption of those nutrients in the diet. So we're learning and some people are doing extremely great work. We want a definitive. We know what you ate.

We know that made it into the milk and we know that's the thing that's going to be exposed to baby. the milk, and we know that's the thing that's going to be exposed to baby. And I think that when we get the tools to keep doing this better and better, we can better understand how what we eat affects how we synthesize milk. Interesting. Yeah, I hadn't really thought about how it is a whole body production effort. It's not just the mammary gland. You mentioned circulation, but of course, diet. Other things we should keep in mind. There are a lot of factors that go into lactation that make it hard or easy, like health of the parent, what's going on in times of infection or other diseases or disorders can also affect what's going into milk. And also, we're trying to get a better idea of not just nutrients, but what if you take

a Tylenol or what if you do certain other things? There's a lot that we are still trying to understand. But I think what's great about it is that we have some of the blueprints on how to ask those questions. And now it's just asking them. So you mentioned that much of your work in your lab has to do with fat content. You mentioned that much of your work in your lab has to do with fat content. And in particular, there's a molecule or a class of molecules I had never heard of until trying to prepare myself to talk to you about this. Am I going to say it right?

Sphinx lipids? Yes, you said it right. I was going to say, are you going to say it right? Yes. If the purpose of this is that more people know about sphingolipids, that would be great. It has such a kind of foreboding name, but it's actually a class of lipids that are involved in many of the processes in the body. They're part of the cellular membrane. They can act as structural molecules and they can also act as signaling molecules. But what is cool about sphingolipids to us is that they're in the fat fraction of milk, they are produced by certain beneficial microbes, and there are also many signaling pathways in us as humans that can actually

accept these signals. So when we're thinking about how diet, microbiome, and host interactions support health, this is actually maybe one of the metabolites or chemical signals that may give us some of those clues. The word itself is a little bit off-putting and intimidating. Sphingolipids. Why would you call them that? Yeah, I think that all came from how difficult these lipids were to study originally. They got this reputation of being very elusive and enigmatic like the Sphinx.

And so that stuck, even though now it's a lot more straightforward to measure some of these lipids. And as more people access the ability to measure sphingolipids, they're finding out how really they're connected to so many facets of our biology. And they're really important mechanistically in a lot of the processes we're trying to understand. Once you learn about the word, you learn about sphingolipids, you can't get them out of your life. You're going to see them everywhere you go. So you have to let me know if that's true. It seems to have such a multifaceted or

versatile role. You said you can use it as building blocks, like structural components. It can be used to communicate information, can be used for building, you mentioned cell membranes. Cell membranes, really important part of the cell. And I think that you can also say that certain structures of sphingolipids can be used as chemical signals between cells and between even microbes and cells in the body. And so that's what we've really been trying to think about in the case of how do we know where something in the diet goes. My lab has really been trying to think about

how do we know which nutrients interact with the microbiome so that we know what are the important microbes that are affected by diet? And then what are the consequences of those interactions. So we have these microbes that may be taking up and transforming these nutrients. What are they making, and how does that affect our health? And I think that is really important in the infant context, because a large portion of milk are molecules that interact with the infant's gut microbiome. You have estimates that almost 10% of the dry mass of human milk is for communicating with the gut microbiome. And we're trying to figure out, are there more

molecules that are doing that? And what are the consequences when you don't have some of those chemical signals that are occurring. They must serve some sort of beneficial function, you might postulate. We'll be right back after this message. Welcome back. So if I'm hearing you right, the most naive view was milk as food. Now we're seeing that milk is not just food to build strong teeth and bones and stuff like that. What I'm hearing from you is that these sphingolipids, as just an example of the cool kinds of molecules in milk they could be, a way for the mom to talk to these bacteria that make up the microbiome.

Possibly, yeah. And that's what we're trying to figure out. And not just sphingolipids, we've also looked at maybe some people's favorite or least favorite nutrient, cholesterol, things that when we consume those lipids, are they interacting with the microbiome? And how is that part of how our health is determined by what we eat? And so we're really at the stage where we're trying to figure out who's important and why they're important in this kind of system. So which bacteria are significant for having effects on our health and

why? What are the mechanisms? So if I can show you something. Oh, you want to show me something? Can I show you something, Steve? Because I think that what we've been trying to do is make it so that you can actually see this happening. So what we're looking at here is a picture of the microbiome. And the microbiome is a collection of microbes. And in this case, this is bacteria, so very small things. And this picture was taken by a microscope that we have in the lab. And what you can see is that there are some microbes that are blue and some microbes that are red. And the ones that are red are ones that we actually were able to introduce a label of a nutrient. In this case, it's cholesterol. And this cholesterol was consumed.

And then we can follow that label. And the label turns out red. So any microbe you see that is red has taken up cholesterol, and anyone that's blue has no interest in cholesterol at that particular time. You're talking about like a label in the sense of radioactive labeling? The same concept, but this is fluorescence. So the red is a red fluorescence. And so that for us is important because it lets us actually identify the microbes that are interacting with what you eat versus the ones that are not. Very cool. Let me just underline this because so much of biology is about seeing things that are hard to see. But it's been a tremendous help in neurobiology and now apparently in nutrition that something that was invisible, you with these labeling tricks can now track and see

what's going on. Yeah, it's why they give out the Nobel Prize for these things, because it helps people like me ask the questions that we want to ask. It seems really simple, but it gives us a little clue that we're going in the right direction. And then we can ask a lot of things that may not depend on the fluorescent signal, but allow us to get into some of the chemical pathways that are involved in it. And then we have machinery where we can physically separate them and we can identify all the microbes that are red. And so you may think that this is trivial, but this actually helps start the basis of some of the questions that we're talking about. Are these nutrients important for the microbiome? If they're being consumed and they are being transformed, at least they're

having some sort of effect. Okay. The whole thing with the microbiome, maybe it's not so new to you, but for a lot of us out there in the public, we haven't really been thinking about the microbiome until, I don't know, the past decade or two or something. What's cool about studying the microbiome and teaching it here at Cornell is that when you walk into a class, people believe you when you walk in. They're like, microbiome is important. You don't have to sell that. My gut health is my whole health. sell that. My gut health is my whole health. When I ask students in the class, how many of you have taken a probiotic or how many have you done, how many of you have eaten a prebiotic, all the hands

shoot up. And so there's a sense that it's very important. But what specifically is important? What is it that we eat that is actually having these effects? And so it lets us know, you know, Steve, I don't know, have you ever taken a probiotic? I think I have. I'm mostly familiar with it because I often give them to my dog, Murray. Yes. When Murray's taking these probiotics and things like that, how do we decide which one's the one that's beneficial? To give those answers, we have to start at the basics of like, I don't want to simplify it too much, but what are the good microbes and what are the contexts that they are acting in support of health versus not?

And so if we want to know that probiotic that we're taking is going to work for us, I think we need to know some of these very specific interactions on the molecular and biochemical level. Now, does it count that I eat yogurt? That counts. You can do probiotic, prebiotic. In nutritional sciences, we really think about how diet and the microbiome are very well connected because sometimes you can have microbes, but they need certain nutrients to survive in the gut.

And if you don't provide that, then there's no point in taking that probiotic, potentially. And then there's also nutrients that you may be taking, and you may think that they have a beneficial effect. But if you don't have the microbes that are actually acting upon that dietary substance, then you're also not going to get that health effect. Famous case would be dietary fiber. So we do a lot of asking who and what did they do? And that actually gives us a lot of insight into what might be important for promoting health when we think about diet microbiome interactions. So in speaking about fiber, let me shift gears slightly to a different study that's come out of your lab having to do with diagnosing infant illness based on their poop. If I can say it that way.

You got right to it, Steve. You're a parent. You've looked at a few diapers in the years. And were they all the same looking? No, they were not. And when we talk about feeding babies and taking care of babies, one of the big things is that they don't always tell you what they need in the way that you can understand. But there's a wealth of information in these diapers that are basically microbes and metabolites. And if we can understand what's going on here, then we may have clues into how baby's health changes in real time. Then maybe therapeutics

can be more responsive if we have more information about what a healthy diaper is versus what a not so healthy diaper is. We all have maybe Googled, is green okay? What's going on here? It's actually one of the most popular parent searches out there. And we think that we can put a little more rigor into that because we have the tools to actually maybe determine, is this okay or is this not okay? The great thing is that you're never at a loss for samples. So our group and many other groups around the world have really been able to start to ask these questions about how do we understand infant health through the development of the microbiome in the first few months of life. So what exactly is the kind of study that you would do? So you collect some poop and then what would you do to analyze it?

We can isolate the microbe and then we can use DNA sequencing to understand what the classification of that microbe is. And then we can also look at all of the small molecules or chemicals that are in there as well. So that's maybe a combination of things that were digested, things that were not digested, intestinal cells. We can also measure that and try to interpret what that may mean in the infant context. One of the most famous examples of it is that in certain infant liver diseases, they stop making bile. And so if you can measure bile and it's there, then great. And if you measure bile and it's not there, that's indicative of that. But also the stool turns a completely different color when bile's not there. But on the day-to-day,

there's probably a lot of information that we're missing just because we haven't been able to decode it yet. All right. So it sounds like we could spend many shows on the microbiome itself, but I wanted to get back to milk because there are so many fascinating things to discuss with you here. What is a typical amount of time to be feeding in that way? When is it time to get back to milk because there are so many fascinating things to discuss with you here. What is a typical amount of time to be feeding in that way? When is it time to move on to other kinds of nutrients? That's a good question because I think it's good to orient it. So the recommendations by the World Health Organization and the CDC would be exclusive human milk feeding for six months, and then the introduction of complementary foods,

different people have different ways that they do it, but still having milk as the main source of calories for the infant for a while, and then the introduction of cow's milk, potentially at one years old. And then also the encouragement of any human milk feeding if that works for you. So there's not really a time that you have to cease that necessarily. But I think you're about to ask me the trillion dollar question, what are the long-term health consequences of exposure to human milk versus exposure to infant formula?

By feeding baby milk today, am I starving off allergic asthma in five years? Or are there developmental processes that are really time dependent that are very important? And are those things that can lead to lifelong health? And could we actually determine what those are so that they're in every single form of infant nutrition? I think about this a lot, about what's important. Even as parents, you think, geez, if I dropped them on their head yesterday, was that important? Or was it not? Or no, they licked that off the ground. Was that

important? What are the things that I really need to worry about in terms of am I creating the right environment for setting them up for success in the future? And the answer is probably like babies are very robust. So we worry maybe more than we should. And is it too early to answer any of these questions about the long-term effects? Is the subject too young, or do we have some clues already? I think there's some clues. I mean, there are epidemiological studies

that have correlations between feeding mode and outcomes or even microbiome composition based off of feeding mode and outcomes or even microbiome composition based off of feeding mode and outcomes. But I think it's too early because those studies are extremely hard to do. What's really challenging about some of the studies is that feeding babies is very difficult. It's not usually like human milk versus formula or this versus that. There are different times, like you may have gone to three months or you may have gone to six months or there may be exclusive feeding for one month. There's so much variation there that we need to capture if we want to really answer those questions properly. And then we need to be able

to follow cohorts very intensely for a long period of time to start getting at some of those questions. That takes a lot of resources. So in a broader context than just human milk, what if we talk about other kinds of mammalian milk? For instance, a lot of us are drinking cow's milk all the time. And how different is it? Does the milk of some other animals do jobs that human milk doesn't and vice versa?

Yeah, I think that there are some similarities, but there are a lot of differences. If you think about the function of milk, it's to grow a baby of that particular species. And cows and babies are different sizes and they have different growth trajectories. So you can imagine that can be reflected in the milk. So when you think about cow's milk, more protein forward versus human milk, very carbohydrate forward, there's all sorts of different strategies for the transfer of nutrients in different species of animal milk. But cow milk does have a lot of the things that are the building blocks of human milk. So when we think about using cow milk as an alternative, it can make a lot of sense. So typically we drink pasteurized milk. There are people who don't,

right? I guess the difference being if it's pasteurized, you've killed off all or most of the microbes that are going along for the ride, you may have still some of the nutrients. And there's pasteurized human donor milk. So there's a whole thought about how do we think about donor milk and are those live factors in donor milk and also the things that may be denatured in heat, molecules may change their conformation and different types of pasteurization methods. There's a lot of really smart people out there thinking about what are the consequences

of this. Another one that I'm sure is on the minds of many of our listeners has to do with lactose intolerance. I read somewhere that the ability of adult humans to break down lactose, I read somewhere that the ability of adult humans to break down lactose, which is, of course, the primary sugar in animal milk, that's a relatively modern trait. Only something like 6,000 years ago that we started to be able to do it. Historically, only infants had the enzyme lactase that would allow them to digest breast milk. So I guess my question is, if adults of 10,000 years ago couldn't drink milk at all, but now most of us can, with a few exceptions, do we have any idea what instigated this change?

Do we think there's some genetic mutation that was favorable and began to propagate? Yeah, my understanding is that lactase is under a neonatal promoter. So this is a gene that will be expressed during the infancy phase and then that shuts off. But then you can have a mutation that doesn't shut that off and that can allow for lactase to be expressed into adulthood. Some people have done some really good work about the spread of this particular ability based off tracing the genetics of this particular mutation. Some of your microbes can also metabolize lactose. Bringing it back to the gut microbiome, how is that involved in

lactase persistence and such? Interesting. You already touched on this a little, what you brought up about milk versus formula. Certainly many parents or caregivers will be thinking about this. Does your research give us any insight into this important conversation? Yeah, I think if you come to my lab, Steve, we've analyzed every kind of formula that we can get our hands on. We talk about infant formula as one thing, but there are many different formulations. So in our lab, we quantify the milk that we get in, and we also quantify any of the formulas that any of the caregivers may be using. And you can very clearly see the differences in the nutrient

profiles between the different types of formula and also between formula and human milk. And really trying to understand, is there like a central set of nutrients that the microbiome needs to be exposed to? Anything you feed a baby, we'll measure it in the lab. Why it's so hard to talk about the subject is that everybody's evaluating. Like I gave this talk at the Pew meeting and afterwards people are like, what formula? What did I do? I called my wife and I told her that we're doing it all wrong. And I don't want that to be the message. I want the message to be more that people are doing things right and we just wanted more information. I know that there's important issues at stake here for medicine, for population, public health, all kinds of things. But just in terms of the pleasure of being a scientist,

what is it that gives you joy in your research? Oh, wow. So many things. Getting to ask the questions that we think are interesting, and then also working with the team of scientists that I work with to see their creativity and also the resilience, because these questions are hard. The picture that I wanted to show you, the day that we got that picture, standing around and looking at the computer screen and I was like, is this it? Is this what we think it is? That kind of excitement really drives a lot of the hard work that goes into what we do. That's great. Thank you so much. So we've been speaking with Cornell molecular

biologist Liz Johnson. Thanks again, Liz, for this insightful conversation about milk and the microbiome. Thank you so much, Steve, for having me. Thanks for listening. You can find more content, including Liz's picture of fluorescence labeling in the microbiome, at quantummagazine.org. If you're enjoying The Joy of Why and you're not already subscribed, hit the subscribe or follow button where you're listening. You can also leave a review for the show. It helps people find this podcast.

The Joy of Why is a podcast from Quantum Magazine, an editorially independent publication supported by the Simons Foundation. Funding decisions by the Simons Foundation have no influence on the selection of topics, guests, or other editorial decisions in this podcast or in Quantum Magazine. decisions in this podcast or in Quanta Magazine. The Joy of Why is produced by PRX Productions. The production team is Caitlin Falds, Livia Brock, Genevieve Sponsler, and Merit Jacob. The executive producer of PRX Productions is Jocelyn Gonzalez. Morgan Church and Edwin Ochoa provided additional assistance. From Quanta Magazine, John Rennie and Thomas Lin provided editorial guidance,

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