Siobhan: Hello and welcome to another episode of Microbiomedics Podcast. Siobhan: I'm Dr. Siobhan McCormack and this episode is dedicated to the incredible work Siobhan: of today's guest, microbiome science legend, Professor Martin Blazer. Siobhan: Now I'm going to skip over his long list of academic posts, his hundreds of Siobhan: publications, his numerous prizes, because quite frankly it would take too long.
Siobhan: But for listeners new to the podcast, let's just say Marty Blazer is to microbiome Siobhan: science what Elvis Presley is to rock and roll. Siobhan: Professor Martin Blazer, welcome. Guest: Thank you. I appreciate that. Siobhan: Arlos, thanks so much for joining us. I wonder if you could start by telling Siobhan: the listeners where you work and the positions you hold. Guest: Thanks so much, Shiv. I'm a professor at Rutgers University. Guest: That's the State University of New Jersey.
Guest: I serve as the Henry Rutgers Professor of the Human Microbiome. Guest: And I also direct an institute called the Center for Advanced Biotechnology and Medicine. Guest: It's a basic science research institute. Guest: I'm a medical doctor by training, but I'm now very deeply into science. Siobhan: Well, you may have noticed, Professor Blazer, I called the episode Back to the Siobhan: Future with Marty Blazer in reference to the excellent American sci-fi film
Siobhan: of the same name. I don't know if you've ever seen that movie, Marty. Guest: I do. I remember Marty McFly. I remember all the Martys.
Siobhan: That's right. That's right. So for those very confused listeners who don't know Siobhan: what the heck I'm talking about, Siobhan: the film Back to the Future, it follows an American high school student, Siobhan: as you say, called Marty McFly, who's able to time Siobhan: travel using a souped up DeLorean car built by his eccentric scientist friend Siobhan: doc brown now i've managed to borrow an imaginary time traveling delorean car
Siobhan: and i thought it would be an excellent way to explore your life's work are you Siobhan: up for it marty sure sure uh i hope you're not going to regret this but but let's go, Siobhan: it's part around the corner so grab your coffee grab your coat and let's chat and walk, Siobhan: So, Marty, what was high school like for you, and how did you get from high Siobhan: school student to microbiome scientist? Guest: High school, you know, was wonderful and terrible, like it is for everybody.
Guest: But I did survive. I actually had a good time, especially in my last year of Guest: high school. I kind of came into my own. Guest: And I was always good in science, and they kind of pointed me in that direction. Guest: I went off to college. I studied economics. Guest: That was my first degree because I was always interested in that kind of thing. Guest: But I discovered that I would never be a great economist because at the really Guest: high level, it's all math.
Guest: And I'm actually very good in math, but still not good enough. Guest: And so I didn't know what to do. Guest: The Vietnam War was going on. My parents said, why don't you become a doctor? Guest: And I didn't really have many good alternatives. I said, okay, I'll try. Guest: I took organic chemistry, the famous course that makes and breaks students. Guest: I found I liked it. And that kind of settled my fate. I became a doctor. Guest: I worked in internal medicine.
Guest: And the way careers go, I was living in Denver, Colorado. I loved Colorado. Guest: I was finishing my training in medicine. And I wanted to stay in Denver. Guest: And I also wanted to get some more training. I wanted to have a specialty. Guest: So I went to the chiefs of the divisions of endocrinology, rheumatology, Guest: infectious disease, allergy, and clinical immunology to see if they had any Guest: positions for that July. Guest: By this time, it was March.
Guest: And all of them said, oh, no, it's much too late. There are no positions. Guest: And so I decided I was going to do some more emergency room work. Guest: I got my license in Kansas. Guest: Everything was set. And on May 15th, they called me and said, Guest: we have an unexpected opening for position in infectious diseases. Guest: I said, great, I'll take it. Guest: Two weeks later, the endocrine guy called me. He said, we have an opening. Guest: I said, I'm sorry, I've accepted ID.
Guest: Clinical immunology had an opening two weeks after that. Guest: I began my fellowship on July 1, all based on who dropped out of their program first. Guest: That's how it happened. On July 10th, I saw a patient with a weird organism Guest: in his blood, and in his brain called Campylobacter fetus. I knew nothing about it. Guest: And I decided that I'll give a conference about that because we had to give Guest: conferences as trainees.
Guest: And what's better than something obscure that nobody knows anything about? Guest: And as I was doing it, I read a paper written by a local doctor in Worcester Guest: named Martin Sciro, a paper in the British Medical Journal called, Guest: Campylobacter enteritis, a new disease. And that was the cousin of the organism Guest: I was studying. I thought, wow, that's so interesting. I gave my conference. Guest: Afterwards, a very small, petite Chinese woman came up to me,
Guest: Wen Lan Wan. She said, I'm interested in that organism too. Guest: She became my closest colleague for the next 10 years. We started working on Campylobacter. Guest: I went to the Center for Disease Control. Guest: I came back to Colorado. I was on the faculty. I went to Vanderbilt as the chief Guest: of infectious disease. I went to NYU as the chair of medicine. Guest: And now I'm running a research institute. So a lot of movement, Guest: but I've had a long and wonderful medical career.
Siobhan: Ah, it sounds. We nearly lost you to endocrinology then. We're lucky that the Siobhan: right job came up at the right time. Guest: Well, I'm still dabbling in endocrinology because I'm working on obesity and diabetes. Siobhan: Ah, yeah. Everything connects. Well, here we are, Marty. we've arrived at the car park. Siobhan: We're walking up to the DeLorean DMC and she is looking magnificent in this Siobhan: bright morning sunlight. I think you'll agree.
Siobhan: We're admiring the iconic futuristic design that is the DeLorean DMC. Siobhan: And Marty is obviously impressed. He's gliding his hand along the beautiful Siobhan: brushed stainless steel body, which combines futuristic design with unparalleled durability. Siobhan: It's powered by a 2.85 litre V6 engine delivering around 130 horsepower. Siobhan: That's 0 to 60 in eight seconds. Siobhan: But best of all, Marty, look at this.
Siobhan: These gull wing doors, which should, if I get the right button, Siobhan: yes, open upwards and outwards. Siobhan: And I think you'll agree they're visually stunning. What do you think? Guest: It looks good. Siobhan: Yeah. So are you happy to drive? Guest: Sure. Siobhan: Yeah. Okay. Hop in, hop in and we'll work out when we get in there. Guest: Of course, it's difficult driving on the wrong side, but I'll do my best.
Siobhan: We are now seated in the cockpit and Marty's fiddling Siobhan: around working out how the time machine works i think Siobhan: you put the date you want to travel in the box here and then there's this is Siobhan: the flux capacitor which i'm told uh allows the car to travel in time when you Siobhan: accelerate marty to 88 miles per hour so are you ready to go let's go yeah seatbelts Siobhan: on let's travel back in time,
Siobhan: So we've arrived at our first destination. Marty, where are we and why have Siobhan: you brought me to this year? Guest: Well, 1940. 1940, World War II is on. It's the year of the Blitz. Guest: London is in ruins. People have injuries. They get infected. Guest: Infection, in some cases, was lethal because this was the era before widespread antibiotics.
Guest: Penicillin was discovered by Fleming in 1928, but it really didn't arrive very Guest: much until the group at Oxford started making it. Guest: Then they purified it in industrial amounts, and also people in the U.S. Guest: Helped with that as well. Guest: Now, during World War II, maybe in 1942, 1943, penicillin started arriving on Guest: the battlefield and in hospitals and began to save lives. Guest: And it was clear that this was miraculous.
Guest: People who would have died were now living. Guest: And so that's the miracle of antibiotics. And after penicillin came many other antibiotics. Guest: And we are currently in the antibiotic era. It's now more than 80 years later. Guest: And antibiotics are one of the pillars of medicine. Every doctor uses antibiotics. Guest: It affects every aspect of medicine. Siobhan: So we kind of ushered in this golden age of medicine.
Siobhan: I think I remember reading your book about the death rate from babies in around 1850. Siobhan: Can you just outline what a difference it made to infant mortality? Guest: Well, actually, infant mortality has really declined tremendously in industrialized Guest: countries since starting in Guest: the 1880s, 1900 to the present. Most of that was done due to sanitation. Guest: Vaccination, and preventive medicines.
Guest: Most of the decline in mortality, 80% of the decline in mortality in kids happened Guest: before 1940, before penicillin came on the scene. Guest: So penicillin gets a lot of credit, but in fact, most of the improvement in Guest: lifespan comes from these other measures. Siobhan: Wow, I didn't realize it was 80%. So obviously, these drugs can be very effective, Siobhan: life-saving and relatively low in side effect profile. So it sounds brilliant. Siobhan: What's the problem then?
Guest: Well, it is wonderful. There are two problems. Guest: The first problem was recognized as early as 1945 when Fleming won the Nobel Prize for penicillin. Guest: In his speech, he talked about the development of resistance to penicillin. Guest: And what we know is that every time a new antibiotic has been introduced. Guest: The bacteria, some bacteria have become resistant. Guest: And over time, they become dominant because Darwin was right.
Guest: There is natural selection. The bacteria that are resistant survive and the Guest: ones that are susceptible are killed. Guest: So that problem's been around for a long time. And unfortunately, it's getting worse. Guest: But I think that's the smaller problem. Guest: The bigger problem is what antibiotics are doing to our microbiome. Guest: Remember, the microbiome is all the organisms that live in and on the human body.
Guest: They are our companions for life. And the microbes that we carry are not accidental. Guest: We have lived with our microbiomes and, Guest: millions of years, humans and our ancestors. We've evolved, we've co-evolved with our microbes. Guest: That's our microbiome. And they do important functions for us. Guest: They help our immune system. They fight invaders. Guest: They make vitamins for us. They help us digest food. They program the brain.
Guest: This is all part of what the microbiome does. Guest: And antibiotics, which are being given to treat an infection have collateral effects. Guest: They not only treat the organism and the infection, they're affecting all the Guest: microbes in the human body, and they're changing it. Siobhan: Okay, so we're going to leave 1940 and get back in our time machine and go to our next destination.
Siobhan: So Marty, we've arrived at our second destination. What year is it and why have you brought me here? Guest: Well, I brought you to about 1992, a big leap, and you wanted me to focus on Guest: a bacteria called Helicobacter pylori. Guest: So in 1983, two scientists in Australia, Guest: Barry Marshall and Robin Warren, discovered that the human stomach is colonized Guest: by a bacterium, which they first isolated, and ultimately it was called Helicobacter pylori.
Guest: Interestingly, initially it was called gastric campylobacter-like organism, Guest: and that's how I got involved because I was still studying campylobacters at that point. Guest: But Marshall and Warren showed that some people have helicobacter pylori in Guest: their stomach, and I can call that HP just for simplicity case. Guest: They have HP in their stomach, and the people who have it are more likely to Guest: develop peptic ulcers, especially duodenal ulcers.
Guest: And they and others showed that if you eradicate that organism from the stomach, Guest: you change the natural history of peptic ulcer disease. the ulcers generally are cured. Guest: So this was dramatic, really important discovery. Guest: It won the Nobel Prize for them because that was a great discovery. Guest: And I got involved in helicobacter from when I heard Marshall talk about his work in 1983.
Guest: And we developed some of the first blood tests that were accurate to tell whether Guest: a person had helicobacter or not. And that opened up a lot of doors. Guest: And then we started working on stomach cancer because that's another important disease. Guest: And we showed that people who had helicobacter were six times more likely to Guest: develop gastric cancer than people who did not have helicobacter.
Guest: And that, and studies by other investigators, put helicobacter on the map as Guest: a bacteria that causes cancer. Guest: And so here's helicobacter. It's causing ulcer disease. It's causing cancer. Guest: We, at a group in Italy, found a gene, we discovered a gene which we called CAG-A, which kind of. Guest: Differentiated helicobactors into what we'll call them milk chocolate and dark chocolate. Guest: CAG-A positive strains are the dark chocolate strains. They're more intense.
Guest: They have more interaction with the host. Guest: And we showed that people who had CAG-A positive strains were more likely to Guest: develop cancer, more likely to develop ulcers. Guest: So we were honing in on this because most people who have helicobacter have Guest: no disease. They have no symptoms. Guest: And so the question is, why did some people with it get it?
Guest: And so we found one marker, and we've actually found others as well, Guest: that indicates kind of the differences of why some people get sipped and why others do not. Siobhan: Yeah. So I can see why people, a phrase from your book, the only good H. Siobhan: Pylori is a dead one, sounds like a sensible conclusion to come to. Siobhan: And was that where you were when you started researching this organism? Guest: I was never there. I was never there.
Guest: We were seeing its relationship to disease, but most of the people working in Guest: the field were gastroenterologists. Guest: They're interested in clinical medicine. Guest: And I had a background in infectious disease. I'm interested in ecology and evolution. Guest: And the idea that we should get rid of helicobacter, when people started saying Guest: we should get rid of helicobacter from everyone, I was intuitively skeptical. Guest: I thought, why is that true?
Guest: And in a sense, I began looking around to see, is that really true? Guest: Because everything suggested at that time, and we now know, that helicobacter Guest: has been with humans since before we were humans. Guest: We have evidence by inference that it's been present in humans for at least 300,000 years. Guest: Homo sapiens is only 200,000 years. So it's ancient. Guest: It's been in everybody. But the key point is that Helicobacter is disappearing.
Guest: This organism that was universal until about 100 years ago or 150 years ago Guest: has gradually been disappearing. Guest: And over the course of the 20th century, this organism, which was universal, Guest: I repeat, has gradually gone away. Guest: So now less than 5% of the children in the UK or the US have this organism. Guest: That's a huge change in human microecology. The question is, Guest: what are the consequences?
Guest: And one consequence is that idiopathic ulcer disease, the kind that is. Guest: Stimulated by helicobacter is declining, and stomach cancer is declining. Guest: That's actually great news. And that actually, we knew that even before helicobacter was discovered. Guest: We could see the trends, but now we know an important reason why.
Guest: But at the same time, other diseases are increasing, such as diseases of the Guest: esophagus, reflux esophagitis, or GERD, as you call it in England, we call it GERD. Guest: First discovered in the 1930s, increasing dramatically. Guest: In your practice, you probably see lots of patients with GERD. Guest: Then in 1950, Sir Norman Barrett discovered a kind of dysplasia in the esophagus, Guest: which we call Barrett's esophagus, which is a consequence of GERD.
Guest: And then in the 1970s, we began to realize that there was a rise in a kind of Guest: cancer that was rare called adenocarcinoma of the esophagus. Guest: And now that in many parts of the world, that's become the dominant form of esophageal cancer. Guest: So this trend, Gord-Barrett's cancer, played out over the course of the 20th Guest: century, and it's still increasing. Guest: It's still the most rapidly increasing cancer in the United States.
Guest: So this happened as helicobacter was declining. And we began to look to see, Guest: is there any relationship? Guest: And in fact, in multiple studies, we found an inverse relationship. Guest: People who had helicobacter were less likely to have these conditions of the Guest: esophagus than people who did. Guest: So that suggested that helicobacter, while bad for your stomach,
Guest: is good for your esophagus. And that helps us tie together these two big megatrends, Guest: the decline in gastric cancer and the rise in these esophageal cancers. Siobhan: Is that what you mean by amphibiosis, this idea that an organism, Siobhan: it's context-dependent as to whether it's beneficial or dangerous for the host?
Guest: In the 1960s, a microbiologist named Theodore Roseberry coined the term amphibiosis, Guest: and that's a biological relationship in which there can be damage or pathogenicity Guest: or benefit or symbiosis, Guest: depending on the context. Guest: So an organism like Helicobacter, in one context, in one person, Guest: it's bad for you, and in another person, it's good for you. Guest: And there are many other examples of that.
Guest: So that, in fact, we think that's a general phenomenon of the microbiome, Guest: that many of the organisms in our microbiome are beneficial to us, Guest: but they have cost, so that when your appendix burst, those organisms will kill you. Guest: Same organisms that are making vitamins for you, they'll kill you. Guest: The organism in your mouth, the alpha hemolytic strep in the mouth that helps Guest: you fight the bad streps, if it gets on your damaged heart valve, it'll kill you.
Guest: So this is, in part, this is how nature organizes things. Guest: We carry these organisms. They benefit us. They also have cost. Siobhan: Okay, Marty, we've got a lot more to cover. So let's get back in the DeLorean Siobhan: and go to our next destination. Siobhan: So we've arrived at our third stop. Siobhan: It's 2006, I think, is this New York University we're at, Marty, now?
Guest: So Siobhan: What's happening now i think you moved here in 2000 so what's happening here Siobhan: in terms of your research and career progression. Guest: Well in 2000 in 2001 shortly after i i uh moved to nyu i met a medical student Guest: albertine beard and i told her about an idea i had that uh. Guest: That microbes have something to do with human height because we all know that Guest: people have been getting taller.
Guest: And we developed a paper called The Ecology of Height, the role of microbes in human height. Guest: And we present evidence that this rise in height is not something inevitable. Guest: It's not the first time that it's happened, but human height has varied over time.
Guest: And we make an argument that it actually has to do with the microbial populations, Guest: especially the microbial populations early in life, because most of adult hype Guest: is determined by the time that a person is two and a half years old, not later. Guest: So this really got me thinking about the role of microbes in human biology. Guest: And in 2006, I wrote a paper called Who Are We? Guest: And it was about the biological relationship we have with our microbes.
Guest: And the point of that paper was that we are the combination of us and our microbes. Guest: And our microbes are our partners, and they are fulfilling our physiology. Guest: And that if our microbial populations are damaged, there will be problems. Guest: In 2009, I wrote a paper with Stan Falco, same thing. What are the consequences Guest: of our disappearing microbiota? Guest: Because as I told you, Helicobacter pylori was disappearing, this ancient organism.
Guest: And I thought if one organism is disappearing, probably there are others. Guest: And in fact, unfortunately, that's true. We now know. Guest: Present 2025, we now know that there have been many organisms have disappeared. Guest: If we compare the diversity of our gut microbiome to uncontacted Amerindians Guest: in the Amazon, we've already lost 50% of our diversity. Siobhan: Wow. So it really is the silent extinction. Guest: It is. It is. And by the way, we haven't discussed this.
Guest: You talked about the book. there's actually a film called The Invisible Extinction. Guest: I don't know if you've seen that. It's available on Amazon. Guest: After Missing Microbes was published, two filmmakers approached my wife and Guest: I, and they said, we think there's a movie there. Guest: And so they worked on it for seven years. Guest: That film came out two years ago. It's won some awards. Guest: It's available in many parts of the world.
Guest: And the film isn't perfect, but I think it's actually pretty good. Guest: It's for the general public, the invisible extinction. Guest: And so this was the idea that we have, starting with our understanding of helicobacter, Guest: we now realize that we have lost many of our ancient cohabitants, Guest: organisms that are part of human physiology. Guest: And as we've lost them, now new diseases are arising.
Guest: And that has really, in the 2000s, that has really been my work, Guest: is to see what's the effect of the loss of microbes and the rise of disease. Guest: And being an infectious disease specialist, I focused on antibiotics. Guest: This loss of diversity is not due to a single factor, but antibiotics are a Guest: really important factor because antibiotics are designed to kill microbes.
Guest: And as I told you before, when you take an antibiotic, that antibiotic goes Guest: to every part of your body. Guest: It's carried by the blood to every part of your body, and it affects the microbial Guest: populations that are present there. Guest: And it selects, it inhibits or kills susceptible organisms.
Guest: So actually, in 2002, and maybe that's really the key year, in 2002, I was, uh, Guest: as, as chair of medicine at NYU, I was counseling a young doctor who was thinking Guest: about what field to go into and what, which university to go into for his endocrinology fellowship. Guest: And he wasn't, he wasn't sure about a certain university because all they were working on was obesity. Guest: And I said, well, I said to him, well, you know, farmers feed antibiotics to
Guest: fatten up their farm animals. Uh. Guest: You know, that's well known. That's been known since the 1940s. Guest: And as I said to him, I had a eureka moment. Guest: I thought to myself, aha, maybe that's what we're doing to our kids. Guest: Maybe that's why our kids are getting fat. Guest: And from that point, I began working on the hypothesis that taking antibiotics Guest: early in life could be contributing to obesity.
Guest: And we did studies, lots and lots of studies in mice, including a paper in Nature, Guest: a paper in Cell, showing that taking antibiotics in a critical early window Guest: of development could change the microbiome. Guest: And even if it changed back to normal, the effects, the damage was done. Guest: It altered the developmental process. Siobhan: I wonder if we could just spend a little time, because this is such an important
Siobhan: point. It's astonishing that feeding antibiotics to animals increases their weight. Siobhan: It sounds sort of bizarre to people who haven't thought about it before. Siobhan: What's actually happening at a molecular level? Guest: The first thing to say is that if you study the agricultural literature, you can learn a lot. Guest: And what we know, firstly, we know, I think, three important things.
Guest: The first is that it works in just about any kind of livestock, Guest: pigs, cattle, chickens, turkeys. Guest: This is a wide swath of vertebrate evolution. It's not just mammals. Guest: It's beyond that. Actually, it even works in bees. Guest: Second, the agents that do it are antibacterials. Guest: Just about any antibacterial will do it, but not antifungals or antivirals. Guest: They're very specific to bacteria.
Guest: Regardless of what kind of antibiotic. And the third thing that the farmers Guest: found is that the earlier they started the antibiotic, the earlier in life they Guest: started the antibiotic, the stronger the effect. Guest: The effect on how much they grew and what's called feed efficiency, Guest: the conversion of food calories into body mass. Guest: That's what farmers are trying to do. They're trying to fatten up their animals, Guest: bring them to market early.
Guest: It works. And that's why farmers all over the world put antibiotics in their Guest: animal feed because it increases their profit margin. Guest: It brings the animals to market faster. Guest: They use their feed more efficiently. Guest: Now, of course, there's a bad effect from that, and that is that it promotes Guest: antibiotic resistance. Guest: And gradually, in certain in EU and other places, they're trying to eliminate Guest: that with medium success.
Guest: But worldwide, most of the antibiotics used in the world are used on the farm Guest: to fatten up farm animals. Guest: In China, they make 15 times as many antibiotics as in the United States, Guest: and they're selling them. they're using them at an enormous rate and they're Guest: selling them all over the world. Guest: So this is, don't get me started.
Siobhan: So when we consume those animal products which have been, they've been consuming Siobhan: antibiotics, does that pass down to us? Guest: Generally not because in most cases there are laws that there has to be a washout Guest: period, that if you feed the animals antibiotics you can't slaughter them the next day. Guest: Now some, and you can't use the milk that day, there are some exceptions to that. Guest: And I think it used to be worse than it is now.
Guest: But the issue about the farm is that it's an analogy. Guest: If farmers feed antibiotics to young animals and they get bigger, Guest: I think that's what we're doing to our kids. Guest: And that's what we have shown again and again in mice. Siobhan: So again, Marty, what's actually happening? Siobhan: So what is it doing? So it's altering the microbiome and then that is causing Siobhan: an increased absorption or breakdown of foods or what's happening?
Guest: Yeah, well, several things. First, we have to look at the context. Guest: And that is that the microbiome that we have and that our babies have is not accidental. Guest: We have co-evolved with it. And our immune system and our metabolic system have Guest: co-evolved with it. There's a kind of basal programming. Guest: And now what the farmers showed is that with the antibiotics, Guest: you're changing that basal programming.
Guest: So one of the problems is that there are so many effects, it's hard to sort Guest: out which is the single key effect. And I'll think it's one. Guest: For example, by changing the Guest: microbial composition, it changes the energy efficiency of the microbiome. Guest: They're able to hold on to, when you eat an apple, some of those calories are Guest: absorbed and some of them go into your colon and then your microbes ferment Guest: that and they produce energy for themselves and for you.
Guest: And when you take antibiotics, you increase the number of calories that stay in the body. Guest: So that's one thing. And second thing is you're changing the relationship of Guest: the microbes and the innate immune system that has evolved for a certain microbiome. Guest: Now it's got a different microbiome. Guest: There are different immunological programming. One of the things I learned in Guest: economics a long time ago was the idea that you can't have both guns and butter.
Guest: You can either spend money on defense or on consumption. So if you're spending Guest: less energy on an immune system to fight your gut bacteria, then you have more energy for the. Guest: To put into, into fat tissue. Also, we've shown that there are big changes in Guest: the liver, metabolic pathways that are involved in the production of fat and, Guest: and in the transport of fat to the periphery. Guest: So there, there are multiple mechanisms. We're not done yet.
Guest: We, we, we don't have every piece of it nailed, but we've got a lot of, Guest: a lot of the molecular mechanisms in place. Guest: But I just want to segue for a moment because early life is a really important Guest: time for metabolic development. Guest: That's when the body has to decide how much energy to store and how much energy Guest: to spend. And that's what growth is about. Guest: But in early life, there are also immunologic decisions. Guest: What's self and what's non-self?
Guest: What's dangerous and what's not dangerous? The immune system is evolving and so is the brain. Guest: Who's a friend, who's not? So it turns out that the gut microbiome is connected Guest: to all three compartments. Guest: It's connected to the portal circulation for metabolism, Guest: connected to the immune cells in the intestines, in the pyrus patches, Guest: and it's connected to the brain through the vagus nerve hormones and other mechanisms.
Guest: So that's a really crucial junction. Guest: And when we began studying obesity, you know, I already knew that there were Guest: other diseases that have been rising quite a bit, Guest: like asthma and allergies and inflammatory diseases like, Guest: inflammatory bowel disease. Guest: So the hypothesis broadened that it wasn't just antibiotics were not just promoting obesity. Guest: They were contributing to our modern plagues.
Guest: I had the idea for that book, Missing Microbes, around 2006. Guest: It took me a while to get it together, but eventually the book came out in 2014. Guest: And the idea is that by changing the microbiome early in life, Guest: you're affecting how the baby develops, and that has clinical consequences. Siobhan: So Marty, if I can just clarify this. So I was born by vaginal delivery when at the time of my birth.
Siobhan: I'm considered essentially microbe-free. As I pass through my mother's vaginal Siobhan: canal, I would have collected microbes from the vagina, Siobhan: from the perianal region, from the feces, and all those microbes would have Siobhan: been carefully orchestrated pioneers in my gut, and then other microbes join them. Siobhan: That's the genesis of my gut microbiome. Is that correct? Guest: That is absolutely correct, and that's correct for every mammal, not just humans.
Guest: You're talking about 70 million years of mammalian evolution, Guest: and it's actually deeper than that. Guest: Even birds, they poop on their eggs so that they will see the new generation Guest: with their micro-mammal. Guest: There's an intergenerational passage of microbes. Guest: Your question, you've set this up so I can hit the ball out of the park. Guest: So now we're doing something different. We're doing cesarean sections.
Guest: And so the baby is missing that trip through the birth canal. Guest: And in the United States, one baby out of three is born by C-section. Guest: In some countries, it's more than 50% of babies are born by C-section. Guest: C-section has become the new norm. And those babies do not acquire their normal Guest: microbiome. And that initial work was done by Maria Gloria Dominguez, Guest: who happens to be my wife. Guest: And she showed that C-section babies have an abnormal microbiome.
Guest: Together, we showed that their microbiome doesn't normalize for at least a year. Guest: Eventually, it becomes normal. But that first year of life, they're going ahead Guest: with a microbiome that is different than the ancestrally programmed microbiome of all mammals.
Guest: And she has done work to restore the microbiome through something called vaginal Guest: seeding, where the vaginal microbiota is put on a gauze from a woman who's going Guest: to have an elective C-section, and then the baby is swabbed by that. Guest: And she's shown that that already begins to restore the microbiome toward the natural.
Siobhan: That's incredible. So my understanding is these pioneer microbes that you inherit, Siobhan: if you like, from your mother, they're incredibly important to teaching your immune system. Siobhan: So there's this kind of, they're like primary school teachers for your nascent immune system. Siobhan: And so trying to teach your immune system not to overreact, but to be responsive when it needs to. Siobhan: Is that sort of part of what you're talking about? Yeah.
Guest: Absolutely. I think you said it really well, and that's a very nice metaphor. Guest: I'm going to try to use that as well. Guest: That's the importance of good primary education.
Siobhan: So if you're not teaching your immune system Siobhan: what are the consequences so you have a depleted gut Siobhan: microbiome um in say a baby Siobhan: born by cesarean section who's also likely to be given antibiotics um you've Siobhan: got a sort of double whammy there and then if you're adding formula feeding Siobhan: as well um that is uh depleting it further so uh so presumably what you're saying Siobhan: is that the immune system isn't learning,
Siobhan: isn't building up this reference library that it should be, and that that has Siobhan: consequences further down the line. How does that work? Guest: Yeah, absolutely. I think you stated it very well. Guest: It's like the immune system is hanging around with the wrong group of kids, Guest: and they're getting into trouble. They're underreacting and overreacting.
Guest: So even before this connection with cesarean section and the microbiome was Guest: realized, it was known that kids born by C-section had an increased risk of Guest: type 1 diabetes and autoimmune disease, Guest: increased risk of asthma and allergic inflammatory disease. Guest: So there's epidemiologic work showing that C-section is associated with health Guest: consequences. And now we know the mechanism. It's because of their abnormal microbiome.
Siobhan: Okay, so the immune system would be overreacting, so you would get autoimmune Siobhan: diseases, and it'd be overreacting to pollen and sort of peanuts and... Guest: The immune system is very complex, and it has this whole series of checks and balances. Guest: But if it develops inappropriately, in my theory, then these checks and balances Guest: are gone. And so it's not that taking an antibiotic, the antibiotic looks like a peanut.
Guest: It's that peanuts are essentially the innocent bystander. Guest: The immune system is abnormal. It sees a new protein, and it focuses on that Guest: where it shouldn't because the immune system is designed to concentrate on things that are dangerous. Guest: And somehow it sees the peanut as dangerous. Siobhan: So you're saying that there's, obviously you're ringing the alarm bells about Siobhan: this, what you call modern plague.
Siobhan: So there's obesity, diabetes, atopy, hay fever, autoimmune disease, Siobhan: all these things could be related to the consequences of this extinction of microbes. Guest: So let me tell you about a study that I was involved in that was published a few years ago. Guest: It was a study with colleagues at the Mayo Clinic in Minnesota. Guest: As many people know, that's a very, very fine place for medical care.
Guest: Mayo Clinic is located in Rochester, Minnesota, which is in Olmstead County, Minnesota. Guest: And there've been many studies of epidemiology in Olmstead County. Guest: And so when I visited the Mayo Clinic a few years ago, I said, Guest: why don't you do a study of antibiotics in your population? They said, good idea. Guest: So together, we studied all the kids born in Olmstead County over about a 13-year Guest: period, in total about 14,000 children.
Guest: And because almost everyone gets their medical care there, we had very good records. Guest: And so we were interested in antibiotic exposure in the first two years of life, Guest: and then health outcomes from the age of two up to the age of 13. Guest: And so we looked at 10 different conditions, and I'll see if I can remember them. Guest: Asthma, atopy, food allergy. Guest: Celiac disease, overweight, obesity, autism, ADHD, learning disabilities. I think I left one out.
Guest: But the point is that we looked at the data. Guest: It's all blinded data. Guest: And then we constructed a hazard ratio. And for the 10 conditions we studied, Guest: All 10, the hazard ratio was greater than one, and eight of the 10, Guest: it was statistically significant. Guest: And so that was evidence that early exposure to antibiotics increased the risk Guest: for these childhood, was associated with increased risk for these childhood diseases.
Guest: There were dose responses. The more doses of antibiotics, the higher the risk. Guest: There were timing issues about when in the first two years of life, Guest: was it the first six months, or it wasn't the same for each disease. Guest: And there were differences amongst the antibiotics as well. Guest: Now, we did that study. Since then, I've been involved in two other studies
Guest: which are being submitted for publication. One is a study in the UK of more Guest: than a million children. Guest: And we find many of the same findings. And the other is a study in Denmark of Guest: all the children born in Denmark over a 10-year period. Guest: And we find many of the same findings as well.
Guest: So we have an epidemiologic signature that the antibiotics are not just causing Guest: or associated with a single disease, but a variety of disease, Guest: all these diseases that have gone up since the introduction of antibiotics. Guest: Antibiotics are not the only factor, but these different kinds of studies try Guest: to isolate the effect of antibiotics from other things.
Siobhan: So my clinical colleagues would say, look, you've got a bunch of poorly kids, Siobhan: they go to their doctor and they get drugs, including antibiotics this proves Siobhan: that poorly kids see doctors and get given antibiotics not the other way around Siobhan: how do you account for that when you're doing these sort of cohort studies. Guest: That's why we do studies in mice, because in the mouse studies, Guest: the only variable we give are antibiotics or not.
Guest: So, how do you prove causality? A great English epidemiologist was named Sir Guest: Austin Bradford Hill, and he developed nine criteria to look at causal relationships. Guest: And basically, I recently made a table of this. We've just about fulfilled all Guest: of them for obesity and antibiotics. Guest: It involves coherence, temporality, analogy, experimentation, et cetera. Guest: How do you prove that smoking causes lung cancer?
Guest: There are people who smoke who never get lung cancer. There are people who don't Guest: smoke who get lung cancer. Guest: So it's not a one-to-one relationship, but it is a risk factor. Guest: It increases the risk, and antibiotics increase the risk for this wide variety of diseases. Guest: What we're working on now are really addressing many of the same questions that you asked. Guest: We're trying to really pin down the causal relationships.
Guest: We're trying to understand the mechanisms by why one child will get asthma and Guest: another child will become obese. Actually, there's coalescence. Guest: Kids who have asthma are more likely to be obese. Kids who are obese are more Guest: likely to develop asthma or food allergies. Guest: So they're not independent. Guest: So we're trying to understand the causal relationships. We're trying to understand the mechanisms.
Guest: And very importantly, we're trying to understand restorations. Guest: How can we bring things back? How can we give back the organisms that have been lost? Guest: Can we give molecules? Can we give chemicals that will help restore the immune system? Guest: I'm pretty sure that mostly what we have to do is, for these diseases, Guest: it's got to be very early in life. Guest: Because the causation of these diseases, like height, is happening in the first two years of life.
Siobhan: So, Marty, we're going to get back in the car because we're going to go into the future. Siobhan: We've arrived at a date in the future. I want you to tell me what the date is Siobhan: and what you're predicting. Guest: Now, the future, 30 years from now, 2055, what's going on? Guest: Well, I focused initially on these diseases that are happening early in life, Guest: but the world keeps moving ahead despite my best intentions.
Guest: And what we've learned is that there are a number of other diseases that are Guest: growing, diseases in adults. Guest: For example, cancer in general, it's an old age disease. Guest: But there's more and more evidence of certain cancers rising in young adults. Guest: This is across many different cancers. Guest: And the question is, why is that happening? And it's very bad to die of cancer Guest: when you're 80, but it's really bad to die of cancer when you're 40.
Guest: And unfortunately, these early cancers are going up. Guest: One of the areas where the early cancers are going up is stomach cancer. Guest: And there's already some evidence that the people who are getting these cancers Guest: don't have helicobacter. Guest: So helicobacter is bad for your stomach for the classic gastric cancer, Guest: but maybe the organisms that are replacing it in the stomach are generating Guest: this new cancer. We don't know yet.
Guest: It's early, but this is amphibiosis. Guest: So early gastric cancer, that's the first one that got my attention, Guest: but it's happening early colon cancer as well, thyroid cancer, Guest: kidney cancer, are more common in women than men. Guest: So gastric cancer, which is a disease that has been male dominated, Guest: according to the statistics from the National Cancer Institute, Guest: if the current trends continue by 2050, it's going to flip to female dominated.
Siobhan: So when you started, you were a microbiologist, and I suppose you were looking Siobhan: at single microbes, but now you're an ecologist, You're looking at these communities. Siobhan: It must be incredibly complex, big data systems approaches because everything Siobhan: has consequences everywhere in this very complex molecular system. Siobhan: I just can't begin to think how you work it all out. Guest: It's beyond me. I went from studying single organisms and single mechanisms
Guest: to this big ecology thing. And now I'm trying to go back to the singleness as Guest: well because it's important to understand the mechanisms. Guest: I want to get back to molecules, single bugs and molecules, because we can do something about that. Guest: We can give bugs back. We could give genetically engineered bugs back. Guest: We can give molecules back. There are lots of things that we can do. Guest: And so that takes us to 2055. Guest: And so I'm just worried about...
Guest: In 2009, Stan Falco and I showed a diagram in our paper, this idea that the Guest: microbiome is going down by generations. Guest: It's stepping down generation by generation. So now, 30 years from now, Guest: we're one and a half or two more generations. Guest: I'm afraid that it's going to keep stepping down. And so that suggests that Guest: the trends are going to get worse. Guest: We already know that obesity is getting worse all over the developed world and the developing world.
Guest: The same things are happening in the developing world. They just started later. Guest: I'm concerned about that, but I'm particularly concerned about epidemics because Guest: the microbiome is our coast guard. Guest: It helps fight off invaders, and we have depleted the coast guard.
Guest: And so I'm worried, and there have been studies going back to the 1950s that Guest: show that if you treat an animal with antibiotics, Guest: their susceptibility to invading pathogens goes up dramatically, Guest: not twofold, but 100,000 fold. Guest: So I'm concerned that by depleting our microbiome, we're becoming more susceptible to invaders. Guest: And as we have recently seen, we're no more than two days away from just about
Guest: any village in the world. So we're more connected and we're more vulnerable. Guest: And that scenario is something that in Missing Microbes I called Antibiotic Winter. Guest: Actually, Antibiotic Winter was going to be the title of the book, Guest: but the publisher thought it was too scary. Guest: But that book, Chapter 15, Antibiotic Winter, talks about that scenario where Guest: an infection, an epidemic comes, and it's like a river that overflows its boundaries.
Guest: It just keeps spreading because there's no resistance that's my that's my big fear.
Siobhan: So you've got Siobhan: this potential population of poorly people with Siobhan: obesity diabetes autoimmune disease poor immune Siobhan: function when they do get an epidemic Siobhan: they are have the reduced ability to Siobhan: fight it and double whammy is you give them antibiotics and a lot of there's Siobhan: a high higher rate of antimicrobial resistance so you're talking about a scenario Siobhan: of increased morbidity and mortality and sort of almost moving back to where
Siobhan: we started on this journey, Siobhan: which was kind of the pre-antibiotic era. Siobhan: It sounds pretty dismal. Guest: It is dismal. And by the way, I wrote this, this was published in 2014. Guest: You know, when COVID-19 came, we saw that obviously age was a big risk factor Guest: for dying of COVID, but so was obesity.
Guest: So it's already, unfortunately, one materialization of the hypothesis that these Guest: changes, which we think obesity is being driven, at least in part, Guest: by the altered microbiome, is leading to a mortality that was unexpected. Guest: And it's not linear. Guest: It's multidimensional. So yeah, so this is my big fear.
Guest: And this is why I'm talking to you today, because part of my life's work has Guest: become talking to people about these problems, Guest: talking to doctors, talking to scientists, talking to the general public, Guest: so they understand this, that Guest: when you take an antibiotic, actually it potentially has cost for you. Guest: And not only does it have cost for you, but it might have cost for your children,
Guest: because mothers are passing their microbiome to their kids. If the mother's Guest: microbiome is depleted, their baby will be born with a depleted microbiome. Guest: So in my long career, right now, this is the most important stuff of my whole career right now. Siobhan: Yeah, absolutely. I mean, as a doctor, you'll be aware of that phrase, first do no harm.
Siobhan: And there is this tendency where you're thinking, certainly in the 90s, Siobhan: where we used to sort of give out antibiotics, thinking, well, Siobhan: it's not going to do any harm, is it? Siobhan: And you're covering your bases. Whereas now we're looking at a scenario, Siobhan: perhaps it will be in our British national formulary that all these things are Siobhan: potential side effects and that we have to discuss them with patients as they Siobhan: discuss the risk-benefit ratio.
Guest: We have to change the conversation in the consultation room from this might Guest: not help you, but it won't hurt, to this might not help you, and it can hurt. Guest: So we have to balance things better. Guest: If you're really sick, you need an antibiotic. But if you have a mild illness, let's wait. Siobhan: I'm not liking the look of 2055, Marty, so let's get back in the time machine. Siobhan: Let's get back to the present 2025, and let's start looking at some solutions.
Guest: Number one, stop the ongoing damage. Use antibiotics much more wisely than we're Guest: doing. And I've actually devoted a lot of effort to this and studying this. Guest: It turns out that among doctors, there's tremendous variation in the prescribing Guest: of antibiotics. Some doctors prescribe it to everybody. Guest: Some doctors prescribe it very sparingly. Guest: That's everywhere where you look. And so we have to retrain the medical profession about this.
Guest: And we have to retrain the public about the cost of the antibiotics. Guest: We have to avoid doing C-sections unless they're absolutely necessary. Guest: You brought up the issue of formula feeding versus breastfeeding, Guest: which we mammals have been doing for 70 million years. Guest: There are occasionally times when that's not possible. Guest: Formula feeding has cost because breast milk has micronutrients that are not present in formula.
Guest: These are particular sugars and other molecules, and formula just isn't as good. Guest: So we have to stop that damage during the critical period of time. Guest: The first six months of life are the most important point in any baby's life. Guest: Then there are many antibacterials in the foods that we use. Guest: We don't think about it, but the things that are used to increase shelf life are antibacterial. Guest: And now we eat them. What's the effect of those on the microbiome?
Guest: There already have been studies that there are effects and things like emulsifiers Guest: and the kind of food processing that we're doing. Guest: So number one, minimize the damage. Number two, think about restoration. Guest: Identify the key organisms. Maybe we'll give Helicobacter pylori back to people, Guest: and then maybe eliminate it when they're 30 or 40 years old so they get the Guest: early life benefit but not the late-in-life cost. So these are examples.
Guest: Maybe compared to 100 years ago, we do something quite different now. Guest: We do blood tests on people. Guest: Healthy people, we say, okay, we're going to check your blood test. Guest: I think we're going to start checking stool tests. Guest: And we're going to understand what those compositions actually mean. Guest: Right now, there are people who are willing to sell you a guide to your microbiome, Guest: but that data so far isn't very useful.
Guest: But eventually, it will be useful. And a doctor will say, oh, Guest: you have high blood pressure, I'm going to check your microbiome, Guest: and that will determine if you have microbiome A, we're going to give you formulas, Guest: drugs A, and if you have microbiome B, we're going to give you drugs B. Guest: That's going to help decide the efficacy of the drugs, and maybe even the toxicity. Guest: Probiotics. So right now, there are thousands of probiotic products out there.
Guest: Most of them are generally safe, not completely safe. Guest: Almost all of them have been untested for the kinds of things that they're being used for. Guest: There are big placebo effects. I have nothing against placebos, Guest: but if somebody were seriously ill, that wouldn't be the thing to use. Guest: I think there will be really important probiotics in the future. Guest: Those will be developed by medical science.
Siobhan: Marty, this has been incredible. Honestly, I've learned so much. Siobhan: Your book, Missing Microbes, I insist that everyone listening to this podcast goes and buys it. Siobhan: It's absolutely brilliant. I've read it a few times, and each time I read it, I learn more. Siobhan: And I have seen the film that you mentioned, The Invisible Extinction, which came out in 2023.
Siobhan: It's an award-winning feature-length documentary. I think they say something Siobhan: like, Two Scientists Race to Save Our Vanishing Micros Before It's Too Late. Siobhan: So that's you and your wife, Professor Maria Gloria Dominguez-Bello. Siobhan: And it's absolutely fantastic, very engaging, really informative. Siobhan: Marty, honestly, I'm so grateful for your time today and also for your incredible Siobhan: work and outstanding achievements in microbiome science.
Guest: Yeah, I would like to thank you for your very intelligent questions and the Guest: passion that you have and that's that's what's going to make the world go around Guest: and that's what's going to change things antibiotics are terrific discoveries Guest: we have to use them wisely we have to use our brains and you're you're obviously Guest: going to be at the forefront of that.
Siobhan: You are sounding the alarm and we have to respond uh and everyone start by reading Siobhan: the book and watching the film so thank you marty is there anything you'd like to add. Guest: Well i'd really like to take the DeLorean on a final spin. Siobhan: Oh, Marty, absolutely. Hey, we'll even throw in some sound effects. Siobhan: Okay, Elvis has left the building. Siobhan: Well, I hope you enjoyed that conversation as much as I did.
Siobhan: And just before you switch off, I've got one final Marty Blazer gift for you, Siobhan: because luckily, when we were chatting after the interview, I forgot to switch Siobhan: off the recording. Enjoy. Guest: I draw the situation like the proverbial iceberg. Guest: So this is the iceberg about the ecological effects of antibiotics. Guest: The tip of the iceberg that has been visible for a long time is antibiotic resistance.
Guest: We see it. We know it. But the body, like the iceberg, the bigger part is underwater. Guest: It's been silent. And that's the effects of antibiotics on the microbiome. Guest: Those effects could be short-term or long-term. Guest: They could affect metabolism, immunity, neurodevelopment, and then they can Guest: have all kinds of disease consequences. We're just learning about that big area underwater.