Change your bacteria, change your life?

Microbiota, the Immune System, and Emotions

Talking Microbiota with Professor Lowry of University of Colorado

(Photo by Casey A. Cass/University of Colorado)

(Photo by Casey A. Cass/University of Colorado)

Healing Hacker: Hi, this is Denise here with Today we are talking with Associate Professor Christopher Lowry of the Department of Integrative Physiology and Center for Neuroscience at the University of Colorado in Boulder. Thank you so much for talking with me today Professor Lowry.

Professor Lowry: You’re welcome. It’s nice to be here.

Healing Hacker: So, let’s jump in. Can you tell us a little bit about your area of expertise and study? How does that lead us to the hygiene hypothesis? Bridge that gap for us.

Prof. Lowry: I’m a behavioral neuroscientist. That means that I study mechanisms that control behavior, or emotional behaviors, that are involved in anxiety and affective disorders like fear, affective behaviors and also cognitive behaviors. Historically, the focus of our lab was on the brain. More recently, we’ve become interested in questions about how the body communicates with the brain, and then how those signals control emotional behaviors.

Part of that interest arose around the year 2000 when we became involved in studying a bacterium called Mycobacterium Vaccae. Our original experiments were designed to understand how the antigens from the bacteria in the lungs could affect brain function and behavior with a very strong focus on serotonin. So, how did these signals affect the serotonin, which is a neurotransmitter, in the brain.

Even more recently, that expanded to try and understand, not just one bacterium, but communities of bacteria, like what you find in the gut. How do these communities affect the brain and behavior?

Healing Hacker: Ok. So, that leads us to the popular term, the ‘hygiene hypothesis.’ I noticed in some of you writing, that you call it the ‘old friends mechanism.’ Why the distinction? Also talk about that in light of another term you use, ‘old infections’.

Prof. Lowry: Right, the ‘old friends’ terminology was put forward by my colleague and friend Gram Rook at University College London. He’s an Immunologist. He and his colleagues, wanted to distinguish between the original ‘hygiene hypotheses’ and our current understanding of the mechanisms that are involved in the hygiene hypothesis. So, the original ‘hygiene hypothesis’ was based on the observation that, children who had older siblings had protection from inflammatory disease.  They thought that was because the older children were causing more infections in the younger children, and these infections were providing protection.

It’s become clear now that there’s not really any infection, like getting a bacterial or viral infection, that’s protective, per se. It’s the exposure to certain types of microorganisms, many of which are not pathogenic at all, that come from our environment. Now the idea is that if you have older siblings, you’re exposed to more environmental antigens or environmental bacteria that provide protection. So, it’s simply a way of thinking about it differently.

The ‘old friends‘encompass basically three different categories of organisms. One is commensal bacteria that can actually colonize the body. These include bacteria that colonize the mucus layer lining of the gastrointestinal tract, such as lactobacilli.

It also includes what are called the ‘old infections’ and these are basically infections that were transmitted by the fecal-oral route very early in life, in children. What’s common among these ‘old infections’ is that they were highly ubiquitous, so most people had them. But on the other hand, they were infections that were not going to kill the host. That’s what allows these types of infections to be so prevalent throughout human history.

Healing Hacker: What kind of infections would those be?

Prof. Lowry: These include some types of Hepatitis virus, Toxoplasmosis and Helicobacter Pylori… I like Helicobacter Pylori as an example of an old infection because there’s quite a lot known about it. Martin Blaser has written a book about this, Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues, which I highly recommend. Essentially, this is a commensal bacterium. And throughout evolution it was virtually ubiquitous to all humans for sixty six thousand years, maybe over a hundred thousand years. We’ve co-evolved with these Helicobacter species.

Other people have called them not-commensals, but something called pathobions, and this is kind of a mixture between a pathogen and its symbiotic organism. The point is that, Helicobacter is normally present, but under some conditions, which are not entirely understood, these Helicobacter species expand, become pathogenic and cause disease like duodenal ulcers. Which is why starting several decades ago the medical profession launched initiatives to try and eradicate Helicobacter species because of this pathogenic potential.

But it’s an ‘old friend’ for a totally different reason. During early development, these ‘old friends’ bind to immune cells in the body and they activate mechanisms that induce immunoregulation, which is another term for immune tolerance. Some of the pathways involved in this induction of immune tolerance by Helicobacter, for example, have been worked out.

Early in life, when these infections were normally very common; what’s happening is the presence of these bacteria change the function of dendritic cells, which are cells that can bind bacterial antigens. Then these dendritic cells train the immune system to be tolerant. Without that training, you have an immune system developing that lacks immune tolerance. Then you have the potential for the immune system to attack things that should be attacking like yourself, like your gut microbiota, like bacteria that should normally be tolerated but under those conditions are not.

That’s what Helicobacter does early on in life, among all the other ‘old friends’. That’s a good example of an old infection. The last category is environmental bacteria and these include environmental saprophytes, which are bacteria that live in decaying organic matter. They don’t colonize the human body like Helicobacter Pylori does, but throughout human evolution they would have been passing through the human body in large quantities. Because they’re in the water, they’re in the mud and on the food. In the last 50 years with purified water sources and more hygienic food, perhaps even that most people consume less fermented food products….there’s a lack of exposure to these environmental organisms.

Mycobacterium Vaccae is one of these environmental saprophytes. It’s in the water, it’s in the mud and it’s in the soil. Throughout human evolution, we would have been exposed to large quantities. The particular strain that we are studying was isolated around Lake Kyoga in Uganda. It’s kind of the center of human evolution.

Healing Hacker: Just because you started talking about H-pylori, which I have read Doctor Blaser’a book and it’s amazing. You talk about how 10% of our bodies are made up of our cells and the rest of us is comprised of symbionts. What does all this mean given it seems like we are on this gradual campaign to obliterate all germs? H-pylori has been virtually destroyed in the US.  We’re trying to get rid of all germs and all things gross, and 90% of our bodies are made up of that matter. What does that mean?

Prof. Lowry: It means that you might have to think about the self in a different way. The self is not just human cells, but it’s all that these bacterial cells. And like you said these bacterial cells far outnumber human cells. These bacterial cells are not just passive bystanders. They are actually producing chemicals that are modulating our own physiology. They have the capacity to interact with our immune system in ways that can control our physiology, our health, and also our mental health. We’re only now starting to understand some of the mechanisms through which these bacteria are communicating, not just with the superficial layers of the human body, the mucosal lining of the gastrointestinal tract for example, but also, through various mechanisms communicating with the brain and affecting behavior. When we think about these bacteria, we really have to think at an ecological level or community level. These bacterial communities are extraordinarily complex. That’s not to say that there aren’t, I think Martin Blazer uses a term ‘keystone species’. For example, the wolf is a keystone species in its ecosystem. There may be bacteria that are keystone species and have a really dominant effect on both the bacterial community and the host.

But, those distinctions, we don’t really have a good understanding of yet. Are there keystone species in the human gut microbiota? And should we be paying particular attention to those species, or should we just be looking at the big picture?

In terms of the gut microbiota, one clear property of the gut microbiota that is a biomarker of good health is the diversity. That may sound kind of vague. But you can think about in very simple terms – as the number of different species that are present. You may think, why would that even matter? Why would more diversity of species be better? We don’t have all the answers to that, but there are some clear ways to think about this. One is that, if you have a diverse ecosystem of bacteria in your body, then it’s harder for pathogens that are known disease-causing agents to get a foothold and expand and cause their disease pathology.

That’s been demonstrated experimentally in animal models. In other words, one of the common consequences of stress, based on animal studies, is the decrease the diversity of the gut microbiota. When that diversity declines, pathogens that cause pathological physiological changes are able to expand in those models. There’s some empirical evidence that diversity is good, lack of diversity is bad. The problem is that, or the question then becomes – How do we maintain highly diverse gut microbiota in order to have more resilience to pathogens and stressors?

Healing Hacker: It’s interesting because how do we maintain that? I feel like there’s a thrust in our culture here to… everything’s should be antibacterial, everything should be feel nice and clean…. and all sterile the lack of a better word…. and we don’t even know what we’re killing off because now it’s gone. How do we get it back?

Prof. Lowry: For people that are interested in those questions, Martin Blaser’s book (Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues) is a very good resource. Then Jessica Snyder Sachs also has a very good book called Good Germs, Bad Germs: Health and Survival in a Bacterial World. It was published a few years ago. These really get at that question. What are we really doing when we are pursuing these goals of greater hygiene and less exposure to germs or bacteria?

It’s becoming clear that there’s a price. It’s very clear that as a population, we are a much less at risk from dying from infectious disease; which of course is a very good thing and much of that success has been through the use of antibiotics. There is a cost to that benefit though. We’re only now starting to learn something about the cost. One thing to point out is that, when we think about antibiotics that we take when we get prescriptions from the doctors… most antibiotics were to derived from bacteria. This is something people don’t often think about. Bacteria are effectively at war with each other. And these bacteria make antibiotics specifically to prevent the proliferation of competitors that are competing for resources that they need to survive.

Most of the antibiotics that we use are compounds that were isolated from bacteria or other microorganisms that have this antibacterial property. A vast majority of these antibiotics come from the phylum of bacteria called the Actinobacteria.

Actinobacteria bacteria are interesting because these are the environmental bacteria. They’re not all environmental but many of them are and they include the mycobacterial like Mycobacterium Vaccae.

Healing Hacker: Let’s talk a little bit about the sterile mice that had aberrant behavior, abnormal behavior and abnormal nervous system structure. Then you repopulated their gut microbiota before six weeks of age and you were able to kind of reverse all of those abnormalities. If you can talk about that a little bit but also, talk about what that could potentially mean for humans as far as correcting existing issues. What would the theoretical windows be? And what might that look like?

Prof. Lowry: To quickly clarify this, that was not our work. That was work we’ve reviewed and discussed. But, effectively there’s a critical window during early development and in mice it’s the first six weeks of life. In humans, this is perhaps late second trimester or third-trimester extending out the first two years of life. The way we think about this in our lab at the moment is that critical window corresponds with when your immune system is developing the capacity for immune tolerance: the capacity to tolerate pollen, dust mites, other environmental allergens, to tolerate self in the context of an autoimmune disease, and to tolerate, perhaps, the gut microbiota.

Some of the mechanisms are known but there’s a particular type of immune cell called the regulatory T-cell. Production of these regulatory T-cells in significant numbers during that developmental window requires exposure to these microorganisms that promote immunoregulation, like Helicobacter pylori for example. Without that training, you would have a reduced capacity for immunoregulation as an adult. The reason is because that’s when the t-regulatory cells are being born as a cell-type. That’s the developmental window for the birth of t-regulatory cells and seeding of the tissues. At that time, decisions are being made whether to make t-regulatory cells or something called T-effector cells that can drive inflammation. It’s a balance between the anti-inflammatory regulatory T-cells and pro-inflammatory TH 1 and TH 17 type T-cells. We think that’s why that window of time is so critical because the stage is being set for this balance between anti-inflammatory mechanisms and pro-inflammatory mechanisms. As an adult, that doesn’t mean that you can’t modify that balance, you can. But your capacity to modify that balance is reduced because you’ve missed the window for controlling the birth and seeding of all your tissues with these regulatory T-cells.

It’s clear that with the right stimulatory in adulthood, you can promote or activate or even induce a proliferation of these immunoregulatory cells. It’s not that you can’t shift the balances as an adult, but the capacity to shift the balance during development is much greater.

Healing Hacker: Got it. It just seems like you probably have so much more ground to cover than you would have in the beginning.

Prof. Lowry: The stage has been set, so to speak. You have all of these T-cells populating your tissues and that’s a lot of T-cells. That’s what you start with and then you can modify that.   But during development you’re actually determining that ratio. The exposure to these microorganisms is determining whether to bias towards immune tolerance or to bias toward immune activation. You can imagine in evolutionary terms why that’s adaptive.

For a human, the environment during the third trimester drives whether you make regulatory cells or pro-inflammatory cells via the immune molecule environment. Cytokines are molecules that are released from immune cells. Those molecules, whether they’re anti-inflammatory molecules or pro-inflammatory molecules, are helping make the decision about what type of T-cells to produce during the third trimester and through the first two years of life. You can imagine that if the environment, if the mother’s environment is a very pathogenic environment characterized by lots the inflammation, it would be adaptive for the offspring to anticipate an environment that has a lot of pathogens. It may be adaptive to bias toward a more pro-inflammatory immune system. But in the absence of that, the inflammation comes with risks. In the absence of that pro-inflammatory environment, it would be more adaptive to not take the risk of autoimmunity and allergies, etc… and bias toward immunoregulation because the risk of infection and the other consequences of pathogens is lower.

Healing Hacker: I’ve actually heard before that two-year window, but you explained it really well in a way that I haven’t thought about previously. What actions beyond the two-year window can be taken? How does ‘farming the microbiota’ look? How can that be something that could make up ground after that first two-year window if someone’s missed it and they’re an adult or an adolescent?

Prof. Lowry: ‘Farming the microbiota’ is a nice term. Effectively we’re just saying that you’re intentionally modifying the microbiota in a way that’s beneficial. It’s analogous to farming because bacteria have food and nutritional requirements just like we do. There are certain aspects of our diet that can promote beneficial bacteria. An example of that is something called prebiotics. Prebiotics are indigestible fibers from plants typically, that we don’t have the enzymatic capacity to digest, but certain types of bacteria do. An example is Bifidobacteria.

These are members of the Actinobacterium phylum. These are good bacteria. And so by consuming more indigestible fiber, you are feeding Bifidobacteria. One theory is that these, along with lactobacilli, are altering the pH in the gut, making it less favorable for the bad bacteria. You’re basically making decisions to consume more prebiotics or indigestible fibers, in order to promote the good bacteria. Ideally, that will make it less likely that bad bacteria can proliferate and get a foothold.

Healing Hacker: Since we’re made up of 10% of our cells and 90% are symbionts, is it possible to farm that 90% to make up for where that 10% is lacking? Since it seems that we have outsourced so much of our metabolism and our immune function to that 90%. Is it conceivable that, to make up more ground and generate more T-regulatory cells, can we farm that 90% in a way that makes up for where the 10% is deficient?

Prof. Lowry: It’s a really attractive approach. We don’t have the empirical evidence for exactly how to do the farming but, I think the farming is a really good idea. If you think about inflammatory disease, which is basically this scourge of modern urban societies; it’s one of our biggest health threats. There are various ways to approach limiting inflammation. I’ll go in sequence and walk you through the different layers of that onion.

One would be to do what we just said – use prebiotics to promote the proliferation of the good bacteria that can compete with the bad bacteria. That’s a prebiotic approach. Another approach is probiotics. In terms of probiotics, in that case you’re not feeding a whole genus of bacteria or multiple genera bacteria at a community level. You’re adding one or two or ten or more different species and strains that ideally have been proven clinically to have health benefits. There you’re tipping the balance toward bacteria that are known to have health benefits, and hopefully there are some downstream consequences for them to out-compete the bad bacteria.

Some of those probiotics are known to have immunoregulatory properties. In other words, they can promote the proliferation of t-regulatory cells, which shift the balance from inflammation toward anti-inflammatory processes. We’re still learning about which types of bacteria have these immunoregulatory capacities. It’s clear that several of them do. Those are the ones that we’re interested in clinically, in terms of moving forward with clinical trials. A third layer, prebiotic –probiotic, third layer is immunoregulation itself. You don’t have to use pre-prebiotics or probiotics to induce immunoregulation. You can do that by injecting immunoregulation agents into the body and directly interacting with immune system.

Most of our research is using that approach, where we’re not putting things into the gut as a nutritional supplement; we’re actually injecting bacteria into the body. That bacteria then train the immune system to be more tolerant so there’s less inflammation more anti-inflammatory responses.

Healing Hacker: Can you talk a little bit about injecting bacteria and how that modulates the immune system?

Prof. Lowry: Let me come back. Let me mention these other two levels and then I’ll come back that. The other two levels beyond immunoregulation are anti-inflammatory drugs. This has been the historical approach of medicine. For example, TNF-Alpha is a pro-inflammatory cytokine. We know that’s driving inflammation and its part of the disease process. Let’s treat it with an antibody that can block TNF-Alpha. There are several of those sorts of drugs currently on the market.

That’s not a bad strategy. It’s just not a comprehensive strategy because inflammation is not just TNF-Alpha. There are many pro-inflammatory cytokines and not all inflammation providing molecules are cytokines. Histamine is involved in inflammation, prostaglandins are involved… Every time you take a step back, or upstream, in the process, you have the opportunity to control a wider swath of the inflammatory process. With an anti-inflammatory drug targeting a single pro-inflammatory molecule; yes it can be effective. But it doesn’t have the potential to affect inflammation on such a broad level as the upstream levels.

The final level is simply avoiding things through lifestyle choices that can promote inflammation and this includes things in our diet, the amount of sleep that we get, and the amount of exercise.

Going back to the immunoregulation, that’s really where we’ve put all of our effort. This is based on the belief that, if you can promote immunoregulation directly, then you could have a pro-inflammatory gut microbiota or microbiota with pro-inflammatory potential, but the immune system won’t respond because it’s tolerant. It tolerates those potentially inflammatory agents like the gut microbiota, like pollen, like dust mites….

The approach there is simply to directly train the immune system to be more tolerant. We don’t have to be attacking pollen or dust mites or certain types of gut microbiota. The way we’re doing that is by injecting this bacterium that I mentioned earlier, which is Mycobacterium Vaccae. Interest in this particular bacterium arose many years ago, not from my lab but through Graham Rook and his colleagues. They’re immunologists. They noticed that the efficacy of tuberculosis vaccines throughout the world vary depending on the geography. There were some geographical areas where the vaccines were incredibly successful. So they went to one of these areas around Lake Kyoga in Uganda, to try and understand why. It turned out that the shores of the lake were lined with this kind of orange slime. This orange slime turned out to be Mycobacterium Vaccae. Through studying the immunology, they realized that this is a very potent immunoregulation-inducing organism. In terms of tuberculosis, it was acting as an adjuvant because it’s very closely related to Mycobacterium tuberculosis.

It was found, in animal models, that you could give this Mycobacterium bacteria by injecting it weeks before an allergen challenge and attenuate the allergy response. They also showed that it could be given orally, so via the stomach, and it would also promote attenuation of allergy in animal models. That immunoregulation is thought to be dependent on activation at T-regulatory cells, but it’s known to be dependent on the anti-inflammatory cytokines like Interleukin-10 and TGF-beta, which I have mentioned before. If you’re talking about inflammation those are the good cytokines. They keep inflammation at a reasonable level. That’s really where the focus is now – if we can enhance immunoregulation and suppress inflammation, can we see health benefits.

And of course the previous work was done with allergy models. My lab is interested in psychiatric disorders. You might ask, “What does this have to do with psychiatric disorders?” It’s becoming clearer that many anxiety and affective disorders, like posttraumatic stress disorder (PTSD), depression, bipolar-depression… are associated with exaggerated inflammation. There is some evidence that if you have exaggerated inflammation prior to a stressor or trauma, then that increases your risk for going on to develop PTSD. It’s also very clear that when people are exposed to a trauma, some develop PTSD and some don’t. In fact the vast majority don’t develop PTSD, only a minority do.

If you compare those groups, it’s clear that the ones that go on to develop PTSD have exaggerated inflammation. The same is true with depression. A study involving over 3,000 people, so a huge study, at Whitehall showed higher levels of two pro-inflammatory molecules, Interleukin-6 and CRP (C-reactive protein), correlated with a greater risk for depressive symptoms 11 years later.

There is a more recent study that was done in Bristol in The United Kingdom, which is where I worked for 12 years. It’s called the Avon Longitudinal Study. It’s a study of developing children. They measured Interleukin-6 in nine-year-old children. Then they looked that depressive symptoms and psychotic symptoms at age 18. And again, it was the children that had elevated Interleukin-6 at age 9 that went on to develop depressive and psychotic symptoms at age 18.

It looks like a risk factor. Now obviously we have to point out this is just an association. There are many other explanations for why that might predict future psychiatric symptoms. But it’s certainly consistent with the idea that this is a risk factor. And, if it’s a risk factor – it’s a risk factor that we can do something about. We can’t do much about the genetic predisposition for psychiatric disorders. It’s much harder to stop warfare at a societal level and prevent trauma. Other risk factors for psychiatric disorders include recent stress but, stress has an inflammation component. We think that inflammation component is part of what’s determining whether someone is going to develop PTSD or not – develop depression or not… That’s something that we can do something about ahead of time. We can enhance immunoregulation and decrease the amount of inflammation in response to a stressor. That’s the theory behind what we’re doing.

Healing Hacker: Is this the probiotic work that you’re talking about because, I know that you mentioned when we were communicating that you’re now doing probiotic work. Is that what you’re talking about?

Prof. Lowry: It’s all related. I’m referring to the work with Mycobacterium Vaccae as an antigen, so injections. That’s a heat kill preparation so; we’re not actually injecting live bacteria. It’s killed, so it has all the molecules that the bacterium would normally have. These molecules then act as antigens and train the immune system. But it’s not living; and so, it’s not going to proliferate. There’s also value, as we mentioned, in thinking along the lines of probiotics, particularly probiotics that can induce immunoregulation – we have submitted grant proposals to look at specific probiotics in terms of their ability to either protect against psychiatric disorders or treat symptoms of psychiatric disorders. What’s not known about the ability of probiotics to enhance immunoregulation, is which species are most effective? What strain of those species is most effective? How much of it do you need to consume? How often do you need to consume it? Are the immunoregulatory effects dependent on some other factor?

There’s a critical thing to understand about probiotics. There’s a very discrete barrier between the lumen of the gut, or the center, where most of the bacteria are living, eating and reproducing. Then there’s a mucus layer that lines the gut. This mucus is a fairly effective barrier to a lot of species, but some species can colonize that mucosal layer. And they can live and reproduce in mucosal layer.

Those are the colonizing bacteria. They’re more likely to be effective at immunoregulation because somehow bacteria have to communicate with the host immune system. The gut has evolved ways of enhancing that communication so there are specialized cells in the epithelial layer lining the gut that have extensions out into the gut lumen. They essentially sample the content of the gut lumen and then present those antigens to the immune system on the other side. Even dead bacteria can communicate with the host immune system through that mechanism. But, the question is:   Are there specific types of bacteria that are more effective at communicating with the immune system through those mechanisms?

H. Pylori is interesting because it actually burrows through the mucus layer and it attaches to the epithelial cells… to your cells. There are some strains of Helicobacter pylori that actually inject bacterial components into your cells. That’s a very direct way of communicating with the host’s cells… attaching to those cells and then injecting material.

It’s also known that our immune system is monitoring those Helicobacter. So, if you look at the lining of the gut, immune cells aggregate around those Helicobacter implantation sites and presumably there’s a communication or dialogue going on between Helicobacter and our immune system. They are talking to each other; that’s why they’re aggregating there. It may be that the immune system is in part keeping Helicobacter from proliferating or doing other things that it shouldn’t be doing to compromise our host. We simply don’t understand those questions at that fine grain detail. But, you can see how probiotics even could affect the host immune system. Those are just a few examples.

Healing Hacker: I have a question about probiotics. My understanding is that most probiotics that we take, they don’t colonizing in the human gut. That’s why you have to keep taking them. You mentioned potentially the more effective ones would be able to live in the mucus layer of the gut. Are there even probiotics that do that?

Prof. Lowry: Yes, certainly. There are probiotics in the market. You can even go to Walgreens and buy some probiotics that are known to colonize the mucosal layer.

They’re known to be immunoregulatory. They’re available commercially. But the evidence that they have the types of health benefits that we’re looking for, in terms of being anti-inflammatory or immunoregulatory, we still need to develop that evidence-base before we can recommend you should be taking this probiotic if you have PTSD, for example, or if you have depression.

I can envision a time when we could say that. We could say, “Okay if you have PTSD, you would benefit from this particular probiotic, or a combination of probiotics…” We can’t do that yet because we don’t have the evidence, but it’s possible to envision a time like that.

I think that even the probiotics that don’t colonize the mucosal layer, have the potential for immunoregulation because of these cells that line the gut. They can actually take those bacteria into the cell, translocate it to the other side of the cell, and then present it to the immune cells. There’s a lot of communication. For that mechanism the bacterial cells may not even need to be alive. They could be dead cells. If that’s true then there really is a constant dialogue between what we’re eating, even if it doesn’t colonize the gut, and what our immune system is doing.

Healing Hacker: Wow… Probiotics as a whole can be overwhelming…

Prof. Lowry: Absolutely overwhelming

Healing Hacker: And good luck finding that strain, it’s like the Wild West a little bit.

Prof. Lowry: It is a bit like the Wild West. I do sympathize with consumers, because I’ve walked down the probiotic aisle at the grocery store and… oh my goodness. It’s not just that you have lots the different probiotics and combination of probiotics, but different companies have different strains. And it’s clear from the work of John Cryan and Ted Dinan, at Cork in Ireland… they have very good evidence that, it’s not just the species of probiotic that’s important but the strain of the species that matter in terms of emotional behavior. And, I wouldn’t be surprised if it’s not just the species and the strain, but how that bacterium is grown. In mycobacteria for example, you get a completely different phenotypic bacteria, rough or smooth variant, depending on how you grow the bacterium. How you grow the bacterium has an impact on what kind of molecules it makes and the proportion of different types of molecules. That’s a level of resolution, we simply haven’t approached yet. That’s probably the level of resolution we will need to optimize the use of probiotics for health benefits.

Healing Hacker: Wow… One final question for clarification, you say strain like for example, lactobacillus acidophilus, are you talking as specific as lactobacillus acidophilus Q135 …?

Prof. Lowry: Yes, it’s the Q135 I’m talking about. Lactobacillus acidophilus is the species, the genus and the species. Then there’s a little number or letter, or a combination of numbers and letters, afterwards that identifies a strain. The strains differ in terms of their genomes, they have different genes, and they produce different molecules. Presumably they have variable metabolism, how variable we don’t know. It’s an empirical question, we have to test that. Those things seem to matter, strain matters. It’s not just lactobacillus acidophilus, it’s lactobacillus acidophilus something… something… something… The strains tend to be proprietary. One company will sell a particular strain, and a different company will sell different strains.

Healing Hacker: One final question and then I’m going to let you go. Going back to that 10% our cells and 90% symbionts. Is that 90% living in our gut or is that all over our body … in our guts and other places?

Prof. Lowry: That’s a very good question. The vast majority is in our gut, but the microbiota as a whole includes all of our tissues. Our skin has a microbiota; the lungs have microbiota. In females, the vagina has microbiota and in males, the penis has a microbiota. Although, I don’t think we know what that is yet. All these mucus layers, all the external coverings, all of these tissues have their own compliment of bacteria. In the skin, different parts of the body have different communities of bacteria…. That’s clear now. What is the contribution of our skin microbiota to our health? Obliviously, it has implications for our skin health, but it could have broader implications as well.

Healing Hacker: Wow… Let me think about it that way and probiotics become an exponentially expanded over-whelmingness…

Prof. Lowry: That’s why there’s so much enthusiasm about the microbiota at the moment. It’s important to emphasize that that field is moving extraordinarily fast. There’s a tremendous amount of excitement. The techniques for analyzing microbiota data are evolving all the time. They are developing, the methods are becoming more sophisticated. The sequencing methods are becoming more efficient, less expensive; more people are getting involved. Although it’s a bit overwhelming because of the scale, because of the fact that it is essentially an ecology question… a community level question… it’s complicated. You can’t ignore the fact that it’s complicated. It’s intricate. But it has vast potential; that’s what’s so exciting about it.

Realizing that potential is all about understanding the specific mechanisms through which these microorganisms communicate with a host; not just with the host immune system, but with other organs like the brain. How does the microbiota communicate with the brain? It’s clear that it does. But, we’re still trying to understand how those mechanisms are involved.

Healing Hacker: I want to thank you so much for talking with me today and I look forward to seeing your work with the probiotics moving forward. What kind of timeline you are looking at?

Prof Lowry: With the injectable Mycobacterium Vaccae, we’ve done a lot of work. We should be able to publish that soon. With the probiotics, we’re really at the stage of designing clinical trials and getting regulatory approval and that kind of thing. And that just takes time; it’s been unpredictable, so we don’t know.

Healing Hacker: With the Mycobacterium Vaccae work that you have done… that’s been with its association with the brain?

Prof. Lowry: Yes. We’re really interested in how enhancing immunoregulation, by using the immunoregulatory bacteria, can affect emotional behavior… with implications for psychiatric disorders like anxiety and affective disorders. That’s our focus.

Healing Hacker: Got it. When is that coming out?

Prof. Lowry: Hopefully within months.

Healing Hacker: Ok. Thank you so much Professor Lowry. I really appreciate it

Prof. Lowry: It’s a pleasure.

Healing Hacker: Have a great day!