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Radio interview with top researchers about the microbiome.

Discussion in 'General ME/CFS News' started by aimossy, Aug 23, 2014.

  1. aimossy

    aimossy Senior Member

    Last edited: Aug 28, 2014
  2. aimossy

    aimossy Senior Member

    This is Science Friday, I'm Ira Flatow.

    Just about every week there seems to be news of how your microbiome -- those trillions of bacteria and viruses in your gut -- play a role in obesity, colon cancer, or your immune system. Now, if your bacteria can affect your health, can't it affect your brain, too? What if the trillions of bacteria are sending signals to your brain, and influencing your behavior? Maybe that gut reaction -- you know, that strange, inexplicable feeling -- is really connected to those microbes talking to your brain.

    This communication is at the heart of new discoveries about the biome and the brain, and that's what we're going to be talking about... you can also reach us, you can tweet us, at @scifri, and go to our website at sciencefriday.com, where a discussion is going on.

    Let me introduce my guests.

    John Cryan is professor and chair of the Department of Anatomy and Neuroscience, principle investigator of the Alimentary Pharmabiotic Center, University College Cork, Cork Ireland.

    Welcome to Science Friday Dr. Cryan.

    Cryan: Thank you, Ira.

    Flatow: Sarkis Mazmanian is a professor of microbiology at Cal Tech in Pasadena, California. Dr. Mazmanian, welcome to Science Friday.

    Mazmanian: It's nice to be here.

    Flatow: Dr. Cryan, let me ask you: our microbiome actually, I understand, produces more serotonin than our brain? A neurotransmitter than our brain? How is that possible?

    Cryan: Well, it's not that the microbiome is producing more serotonin -- there is more serotonin in our guts, way more, than in our brain -- serotonin is a very complex molecule involved in many things, including many aspects of digestion. But what we do know is that the microbiome can also produce -- certain bacteria can also produce not only serotonin, but almost every neurotransmitter: dopamine, and GABA, and all of these neurotransmitters, and can also influence the concentrations of how they're being produced by their own hormonal producing cells, like the enteroendocrine cells in the gut. So, yeah, basically the microbiome is like a factory for producing lots of different neuroactive agents, and we're slowly getting to grips with this, although we're a long way to go to try and understand what (Mark Light?) calls the microbial endocrinology of this interaction between these neuroactives and the actual gut itself, and then how that can signal to the brain.

    Flatow: Yeah, so what are they doing with all these neurotransmitters?

    Cryan: Well, you know, bacteria use them for different things, for different aspects of survival for themselves, things like acid tolerance and a variety of other functions that are specific to the bacteria, but the question is have they evolved to produce these. We're not clear in terms of, you know, how they can activate the [enteric?] system, if the gut becomes leaky, perhaps, and then signals to the brain. But that's the big, black box -- and I'm sure Sarkis will want to talk on that, too -- is how we get from things happening locally in the gut to the brain.

    Flatow: Yeah. Let me go to Sarkis. Dr. Mazmanian, why should there be a connection -- why should there be a connection -- how is there a connection between the nervous system and the microbiome?

    Mazmanian: The connection is something we're still exploring, but there are probably multiple mechanisms by which the gut can communicate to the brain. So John has shown elegantly that certain bacteria signal through the vagus nerve -- which connects the [enteric-?] system to the central nervous system -- so there could be direct neuronal connections. But there are other mechanisms: metabolites -- which are small molecules released by gut bacteria or by the gut itself in response to bacteria -- can travel through the circulation, and presumably get into the central nervous system, the brain, and the spinal cord. Other mechanisms exist in terms of microbial molecules, larger microbial molecules, that may also get through the circulation into the central nervous system. And finally, there is some evidence, albeit it's preliminary, that immune cells can traffic between the gut and the brain, or the central nervous system. Many, in fact most, of our immune cells, are in our digestive tract -- something close to 70 percent of our T cells and B cells are our digestive tract, and they're constantly circulating from our digestive tract to other parts of the body. So in theory there are multiple mechanisms by which gut -- the gut -- and gut bacteria can communicate, can talk, to the brain.

    Flatow: Huh, all coming from the gut, and moving around the body. Hm.

    Mazmanian: Yes, yes absolutely.

    Flatow: And is this fertile ground, is this like a whole new area of research that we have not really tackled in any depth before?

    Cryan: Yes.
    Mazmanian: Yes, the entire area is very new in terms of not just looking at the gut-brain connection, but in terms of studying beneficial bacteria themselves. For many years, microbiologists have predominantly studied pathogenic bacteria and infectious agents, but in more recent years there's been an appreciation that beneficial organisms are not just benign or passing through our system, but they're actually manipulating or controlling certain aspects of our biology, and initially, as you had mentioned, people had studied the connection between gut bacteria and the immune system, which is what my laboratory has studied for many years, as well as the metabolic system in terms of obesity, but more recently, pioneers like John and others, have shown that there are connections between gut bacteria and the nervous system. Once again, very, very new area -- the entire field is no more than ten years old.

    Flatow: Dr. Cryan, you want to jump in there?

    Cryan: Yeah, no - I agree with everything Sarkis has been saying. It is a very new area, and there is plenty of healthy skepticism still out there, which is always good in the field, and it kind of, you know, over twenty years ago, people didn't really believe that the immune system and the central nervous system had any really important interactions, and over the past two or three decades that has really emerged as a big area. So now we're having a new player to that. We've always appreciated that the brain and the gut talk to each other, because in the fields of like appetite, and food intake, people have long known that, but the question now having the microbiome as a player, we're beginning to see how this could play.

    I kind of date a lot of the modern work that we're doing to about just ten years ago, when a paper came from Japan which showed that mice that lacked bacteria had a much greater stress response. And that kind of took a while for people to go through who were interested in stress neurobiology to say, "well, you know, what are the bacteria doing that's helping you have a proper stress response?" And that allowed us then to really look at this. We were interested in early life stress, and we showed, about five years ago now, that if you were stressed early in life that you had a lower diversity of bacteria in your gut when you grow up, and changes in behavior. And so that allowed us and then others, groups in Canada and in Sweden, and Sarkis' group, and others, to really, to move forward with this. But it's a paradigm shift in how we're thinking about neuroscience. You also have to remember that in medicine, the fields of neuroscience and microbiology don't talk to each other that much, in terms of both at an academic level, and in research. And we have focused a little bit on things like the neural consquences of the HIV virus, or other parasitic infections, but now, as Sarkis was saying, the positive effects of bacteria are starting to emerge.

    Flatow: So you could really influence how you feel, what you eat, whether you're fat or thin, but all controlled by what your bacteria like, by keeping them happy? They may say, "hey, feed me this, it makes me happier," and that influences maybe how you feel, or... ?

    Cryan: Well that's where the evidence... that's where the field is moving, but we're not there yet. You know, we have a long way to go, and that's something we also have to do is manage expectations -- there's a lot of hype in the field as well, and we have to be clear that a lot of what we know about brain microbe interactions is still only from animal studies, or preclinical studies, and that there's very little clinical human data out there yet. But I think it's a very exciting time in terms of this, and, you know, there isn't, uh.... there's a lot of potential for having... understanding diet-microbe interactions that may have positive effects on mood.

    Flatow: Let's go to the phones. Let's go to Apama in Dallas, hello, welcome to Science Friday.

    Caller: Hi there. This is very fascinating to me, I just went on the radio as soon as the topic came in. For many years parents who have kids with autism have said there is a clear connection between the gut and the brain. Can your panel show... shed some light on any research that they have done, and I mean, parents who have autistic kids they would swear by it, that there is a strong connection between the gut and the brain, and is it... new research is very interesting, and could this be the breakthrough for all the parents who are looking for answers.

    Flatow: Yeah, let me get an answer. Sarkis, what do you think?

    Mazmanian: Yeah, this is something that my group has recently studied and published in mouse models, so we need to take the findings and the research with a grain of salt, but what we did show is that in animal models of autism, that we were able to reproduces some of the phenotypes shown in humans -- as you mentioned, some of the gastrointestinal phenotypes, such as constipation and leakiness of the barrier. In addition, there's human data showing that the microbiome, the gut bacteria in the gut, of autistic children is different than the best-matched controls, neurotypical normally-developing controls. And that research has always been clouded by the fact that autistic children with GI issues are generally on restricted diets or specialized diets, and of course diet itself can change a microbiome. So it wasn't known if it was the autism that was causing it, or the diet intervention that subsequently causes changes in the microbiome. And what we showed in this mouse model is that we believe it is a link between the disorder, between autism and changes in the microbiome, because all of our animals are on the same food, yet the mice with behaviors that are consistent with human autism have changes in their microbiome, and they also have these GI abnormalities, such as leaky gut, such as the constipation similar to that in humans.

    Flatow: Could you... can you change the bacteria and alleviate the symptoms?

    Mazmanian: And that was my next sentence: and so we took the research one step further, and we asked, "if there is this abnormal change in the microbiome, can we restore that through probiotic treatment?" Now I use the term probiotics here loosely-- the organism we used is one from the human gut, it is not a commercially available organism. But what we did... the experiments that we did in animals is that we introduced this organism to the "autistically-behaving" mice, and were able to restore both the GI deficits and the behavioral deficits.

    Flatow: Wow. Wow. We're going to come back and talk lots more with John Cryan and Sarkis Mazmanian. Talking about the human microbiome, and all the consequences about it in the future. Stay with us, we'll be right back after this break.

    This is Science Friday, I'm Ira Flatow, we're talking this hour about the microbiome, how it might influence our brain, our behavior, our diet, our health, our weight -- who knows. It's a bugeoning field now. My guests are ....

    Gentleman, let me go in the opposite direction now. Is there any evidence, you know, kids get a lot of antibiotics when they're young, and those antibiotics kill the gut bacteria. Is there any evidence in animals that that is in fact affecting the health or the moods of the animals, and possible of the kids who get it at a young age?

    Cryan: So uh, we just published a study looking at this giving animals early-life antibiotic exposure, and the good news for parents would be that we didn't find any marked changes in regard to mood or cognitive performance. But what we did find, and this was quite striking, was that there was an increase in what we call visceral pain processing -- how the brain is able to process pain from the stomach. And this is a hallmark, abdominal pain is a hallmark of disorders like irritable bowel syndrome, and then in infants, colic is often seen as a surrogate of irritable bowel syndrome. So it's telling us that there are wiring probably at the spinal level that have gone awry due to early-life exposure to antibiotics.

    And then just recently, Marty Blaser's group has shown also obesity in adulthood in animals that have been fed low-grade antibiotics. So it will depend a little bit on which antibiotics, and the extent, and the timing, but it's something that we do need to be what I would say cautious about, and always be careful about in that regard. Moreover, you know, there are other naturalistic ways that the microbiome has changed, such as if you're born by C-section, or whether you're being bottle fed or breast fed. All of these can interfere with the microbiome composition early in life. And we would think -- and Sarkis' elegant data would also match this -- that this early life brain-microbe interaction is indeed very crucial, because the brain is in such a state of flux that the interactions there are more amenable to be changed, and that might lead to some of the more neurodevelopmental issues that might arise.

    Flatow: Are you able to be specific enough about what bacteria might influence what effect, like create you know, a listing, a sort of periodic table of the bacteria, that if you have this one, you're going to get this; if you don't have this one, you're going to get that? Can you be that specific enough about the microbiome bacteria?

    Mazmanian: Well, there are specific organisms that have been tested, mostly in animal models, and some in humans, that have been shown to affect the various different conditions that we've discussed -- everything from the neurological conditions to the immune and metabolic conditions. But one has to realize that we are all quite different in our microbiomes, and each of us has a microbial fingerprint, and even in the healthy state, and so it might not be a one-size-fits-all where any one single organism is going to be a therapy for, you know, condition X, Y, or Z. I think that there's a lot of personalization between our microbiomes and our genomes, or our DNA and our physiology, and there's a lot of redundancy in this system. For example, as I mentioned, two healthy individuals can have vastly different microbiomes and still be healthy, and if gut bacteria are conferring health, then this suggests that there are different bacteria in different people that are essentially doing the same thing. That being said, it doesn't mean that there won't be certain organisms that might be beneficial to a large population, and we're thinking that perhaps there are certain organisms that might improve subsets of children with autism. But these are all preclinical data at this point -- once again, animal studies and studies that are just moving into the clinic -- and until we see data in humans, I think that one should remain skeptical, one should remain cautious, about their potential outcomes and benefits.

    Flatow: Let's go to the phones; let's go to Pearl in Baltimore. Hi, welcome to Science Friday.

    Caller: Hi, thank you. This is fascinating. I was wondering about your research and the implication for people who have things like Crohn's disease, and also the connection with the high incidence of Crohn's concurrent with things like fibromyalgia, sleep disorders, neural disorders in other autoimmune diseases like arthritis. What are the implications in terms of possibly finding treatments for things like IBD?

    Flatow: All right, thanks for the call.

    Mazmanian: Yeah, this is something once again my group has worked on for close to a decade now, and in many instances, inflammatory bowel disease you mentioned, Crohn's disease, as well as autoimmune diseases -- multiple sclerosis, rheumatoid arthritis, psoriasis -- result from an overactive immune system. In essence, the immune system believe that it's attacking an infectious agent when it's not, and the consequences are collateral damage to the tissue, the host tissue, whether it's in the gut in Crohn's disease, in the central nervous system in multiple sclerosis, so on and so forth, and what we and others have shown is that gut bacteria have a remarkable capacity to balance an immune response without compromising it. And so the mainline therapies for inflammatory bowel disease, for Crohn's disease, are immunosuppressants -- so if it's the immune system that's attacking your tissues, then current medicine's remedy for this is to ablate arms of the immune system, to weaken arms of the immune system. But of course this isn't optimal, because we need an immune system to fight off infections. And once again, in animal studies what we and others have shown is that gut bacteria don't compromise the host, but yet they do balance or suppress the uncontrolled, the unwanted, inflammation. And so of course this show has been focused on the connection between the gut and the brain, but the connection between the gut and the immune system is an area that is much more advanced, and there are already therapies poised for clinical trials for Crohn's disease that are of microbial origin.

    Flatow: In other words, it would be sort of a probiotic addition of the right kind of gut bacteria, that would alleviate the attacking of the immune system?

    Mazmanian: Yes, we can use the word probiotic once again loosely as a beneficial organism, but we and others once again have shown that the organism has his activities, but we've also identified specific molecules from that organism that also has beneficial activities. In fact, it's the molecules from those organisms that are beneficial, that are the ones that ameliorate or prevent inflammatory bowel disease. And if one can give the molecule, in some ways it's better, and one can make the argument that the bacteria would be more potent, but in some ways this is better, because you can dose as much as you want; you can optimize the treatment for different people; and importantly, if there are side effects, then you can withdraw the treatment, as opposed to giving a bacteria that may replicate in the gut.

    Flatow: So how successful have you been with this so far?

    Mazmanian: In animal models, very successful. Once again, it still hasn't been tested in the clinic, but out goal is to have the therapy in the clinic in the next two years.

    Flatow: Hmm. That's amazing... so what else is on... what other... you mentioned the nervous system and the immune system, what other ways is the biome, what other parts of the body, other systems, is the microbiome affecting?

    Cryan: Everything. I think there is, what we've come to appreciate is that the microbiome has an impact on almost every system that we have. And it's just that the brain has been one of the last frontiers in this regard, you know, and we still have to really figure out exact mechanisms of this communication, I think. But understanding how these systems work together to kind of promote homeostasis. And then to think about it from an evolutionary perspective, as to why they have evolved this way, why there has been this mutualistic positive effect of the bacteria on brain function, as well as negative. But the important thing that I would want to stress is that, you know, most bacteria will probably not have any positive or negative effect on brain function, you know. We need to be clear on that -- that we need to identify what is it about the ones that are actually positively inducing effects, and most won't. And that way we can try and hopefully generate what we call psychobiotics, or, you know, positive bacteria that will induce positive effects on mental health.

    Flatow: So there's one question, we have less than a minute to ask it -- and everybody is asking it on our phones -- is there something you can do yourself to promote your micro... you know, your guts, the bacteria there?

    Cryan: Yeah, so a diverse diet is probably one of the best ways, and you know, the diversity in the diet is one of the best things to promote a diverse microbial population. And the more diverse, the more healthy it is. Generally.

    Mazmanian: And avoiding antibiotics, antimicrobials, anything -- preservatives -- anything in the environment that could harm bacteria, would allow your body to develop a diverse microbiome.

    Flatow: Thank you, gentlemen, very much. Sarkis Mazmanian... John Cryan... thank you for taking time to be with us today.
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  3. Sasha

    Sasha Fine, thank you

    Terrific interview, well worth a read.
    aimossy likes this.
  4. xchocoholic

    xchocoholic Senior Member

    It would be interesting to hear what the autism bio medical group already knows about all this too. Tc .. x

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