How Stress Impacts the Microbiome
Pete interviews Dr Armine Zorgani for the second time to get his expert view on all things microbiome.
Stress is a part of the human condition and some stress is beneficial for health whilst chronic long-term stress creates dysfunction and leads to disease. This episode explores the role of stress on the microbiome and how the microbiome mitigate or exaggerates the stress response. As a side note we spend a good amount of time chatting about the vaginal microbiome and giving women some great pearls of wisdom of how to control bacterial issues such as bacterial vaginosis and other vaginal disorders.
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Transcript
Peter Williams 00:03
So hi everyone, and welcome to this new podcast from functional medicine bite sized, bringing up one of my probably top one or two favorite person to follow, favorite researchers, Dr Armine Zorgani. Mate, good to have you on again. I've been trying to get you on for months. I know you're a busy man, so I really appreciate your time. Because I think, you know, there, I think there are a couple of things I think that's changed in medicine, as far as where all the research is exploded. Number one, of course, is the microbiome, which is your expert area. So really appreciate having you on. And of course, suppose the other side is the still the exercise medicine side as well, which we might talk about a little bit of that, about that, with regards to the microbiome. And really, today is introducing, I suppose, how stress, whether that is physiological, psychological, environmental, how they influence the microbiome, and I just don't mean obviously the gut microbiome is the dominant microbiotic sort of area that we talk about, but obviously the body is basically covered with bacterial regions that maybe we can get into a conversation about later on. But look, as I said to you, you are actually certainly one of the more renowned scientists from regards to this area. Can we just start? Because obviously, just to let everyone know, we did a podcast with, I mean, um, last year, which I think was undoubtedly my favorite podcast, simply because your capacity to actually translate the literature into into a little bit more sort of simple statements is fantastic, and I'm sure we're going to get that again. But, but can we just fit the people who maybe haven't listened to that original podcast, can we just get a sort of an introductory understanding of number one, what we're what we're absolutely learning with the microbiome and just how important it is, and just from a numbers perspective, why it's so important?Dr Amine Zorgani 02:16No, thank you so much, Pete as well, for having me again. And it's always a pleasure to be with you and speaking about this topic, although we may think a lot of people know about the microbiome and it's important in health, the data don't show that. There was two very big reports done by one of also renowned foundations and institutes called the Bio Codex Microbiota Institutes, they only do research, the educational research for healthcare professionals and for general public. And they've conducted two independent studies with also an independent institution for statistics. The first one was on 6500 people, and the second one was on 7000 people across seven countries, the States, France, Germany, the UK and so on, so forth, China. And the goal was there, really, to ask multiple questions about the microbiome. When I say the microbiome today, the first thing that comes to mind, as you said, is the gut microbiome. We don't have microbes only in our guts. We have them on our skin, on the oral microbiome, the the vaginal microbiome, the environmental microbiome, even the air microbiome. We do have microbiota in the air which also influence part of our lung microbiome.
Peter Williams 03:36
So can we just go on to that? Because that's a really important subject. And you know, sometimes when I say to people, if you're going to go for a run, why don't you run through the forest, because the microbiome that you might pick up from there is is substantially better. So can you just brief us with regards to how we interact with, with, with, with bacteria on that side. So I think that's a really important part,
Dr Amine Zorgani 03:57
absolutely, absolutely. So I'll finish just want on the numbers these studies have basically showed so from the first one, if you take on the gut microbiome, it is 6000 you might find around like 30% people who actually know what the microbiome means, or gut microbiome means. But these numbers basically decline to reach 17% on the case of vaginal microbiota, 50% of the population is women, and they don't know what the importance of the vaginal microbial as an example, or about the oral microbiota, which is basically connected. And there are some substantial evidence showing that if you have a disrupted oral microbiota, there are many other disease there adjacent to it, like cardiovascular disease. One disease is the killing one. It's called colorectal cancer. Number two cause of colorectal cancer, it's Fusobacterium Nucleatum which is an oral inhabitant. So you get that, you get the picture there. When we come to the how do you actually get these diversive microbes that we're having? It actually depends on who you are, where you live? What's your age? So if you don't have that much of diversity when you are born, the most bacteria you get is basically from your mother. If you're born vaginally, like natural birth, you get most of that microbiota from the vaginal micro fluids, and then the first contact you get is on the skin. So you start getting those skin microbiota also to colonize a bit. And then it comes to breast feeding. So you get, there are microbes even in the milk that the mother feeds to to her baby. And there are some companies actually showing and working on that, how to actually increase those microbes, and so on so forth. So that's the first colonization you get, which is necessary. We know that if you have a bad colonization, let's call it like that, like born on a C section and not breast fed data as well substantial data showing that there is an increased likelihood of these childrens when they grow up to have diverse types of allergies and atopic dermatitis, asthma, and so on, so forth. So the proper colonization is important. When you grow up iIt's the diversity food and so on, so forth. One element, a recent study showed that we actually get 2% of the gut microbial diversity comes the fruits and vegetables we consume on a daily basis. Imagine that that's a 2% that's just coming from your food. If you go back to nature and you immerse yourself in the forest, you play with dogs and or with cats, and whatsoever, you increase your microbial diversity. This is not just hypothetical. This is facts. You take people who live in the jungle like hunter gatherers tribes, you compare them to someone from California, a study guide by Dr Justin sandenberg from Stanford University showed that these people actually living in hunter gatherers, they had 723 different bacterial type because of species, then a one coming from California, because these people lived in that environment, they are immersed with, you know, the diversity of that, and they have less emergence of diseases that we as industrial population actually have all the time.
Peter Williams 07:14
So can we just, could we just summarize that? Because the summary really is, is that, as I try to explain to people, if you're just going to live in a concrete jungle, you're going to miss a lot of your interaction with bacteria. And one of the key aspects that we think about being in nature
is probably that bacterial exchange. And that's why I always say to people, if you're going to go for a run and you've got some woods near you, then go and run in the woods, because the bacterial diversity that's been shown on forest floors are very substantial, and you're breathing that, and that will absolutely help, particularly the microbiome of the lungs, for sure. And the other thing about this is that I think probably what were quite clear is that you're trying to develop as a diverse species of microbes as possible. And as I said to you, as you've just alluded to, you've got to have a good start in life on this because your risk goes up. So if you are C section baby, then we know that the starting point of the maturity of or the starting point of that immune system is compromised, and so that's a really important point to just to allude to. And as you said, I think what that does it leads to inflammatory led and immunologically led risk factors as you get older. So we definitely see this with the atopic and the inflammatory. So asthma and atopic disorders like skin disorders. So I think 2018 I was at an autoimmune conference, and the main autoimmune guy, I can't remember his name. He's, he's an Israeli guy, I think is the guy is Schoenfeld I think his name is, but he did, he was an old boy. I mean, he was, literally, must have been in his mid, late 80s. He did this most incredible lecture with regards to autoimmunity. And he was at the birth of His granddaughter's baby, because new is going to be C section, and he basically swabbed her vagina at birth of his grandson, and put it straight across his mouth so and because he knew that he would be least delivering some of his granddaughters microbes to his new Great Grandson, which I thought was super cool. And then all the other pictures that he showed was the baby being licked by the dogs, licked by the horses, you know, again, because of that microbial exchange. So I think we sort of introduced that. Can we just talk about again? And I know, because I think intro introductions are really important. The reason why the microbiome is so so important, we think, is because of its influence, general influence over humans are diagnosed with that word, diagnosed, that's the wrong word thing to defined as holobiont arent they - if you're like a super organism, different species living together for the greater of the good, but we're dominated in that relationship by microbes, as far as numbers. So can you give us just an indication, not just of numbers, but also of the genetic influence on that
Dr Amine Zorgani 10:34
Absolutely, just like to also to scare every C section, baby, there's, oh my god, I'm gonna get sick when I get older, there are also C section babies who aren't breastfed, and they are very fine (agreed) that some microbial diversity can also occur after one year. So if you take a C section and normal birth, you would see that, okay, the normal birth has a faster microbial colonization and establishment where the C section is is much lower, but at some point they they reach right. But are there are some cases when the C section baby microbiota don't really get that kind of pickup of diversity because of mostly socio economical reasons, where they live and how they're raised and so on so forth. And that's why breastfed and normally birthed is the most favourable.
Peter Williams 11:28
the most favorable let me just confirm that. Again, everything that we talk about is increased risk or decreased risk. In in the studies, that doesn't mean to say, because you're a C section baby, that you don't have any problems at all. It just means that we know in the literature, the risk is greater within those populations.
Dr Amine Zorgani 11:47
Spot on, spot on so when it comes to the to how this holobiant actually functions, if you speak about the microbiota the gut, let's say, just to make it simple for people to understand one of the most studied organ, and then you want to quantify it, these gut microbiota, these bacteria in our instance. So we say, okay, let's confirm or clarify the gut microbiome doesn't mean only bacteria, it also means viruses, fungi and so on and so forth. But we are mostly studying bacteria because they are mostly dominant. But there is another element that comes on the bacteria, called bacteriophages. This is like viruses that actually connects to the bacteria, which also controls their presence and their composition and their load in our intestine. But let's if you speak about the bacteria as a system in your intestine, you have between 1 to 1.1 kilograms. That's basically the mass of these bacteria from a mass perspective. Now, if you speak about how much of cells of these bacteria we have against human cells, you would have, you know, original studies or original mas. They said, for one cell, human cell, we have 10 cells of bacteria. This is was hypothetical, and there are other studies basically did the actual math and went really deeper. We're more towards one human cell to 1.3 microbial cell. But when it comes to the genetics, if you take a human cell and then you take a microbial microbiota cells, you would find a completely different balance. You would find, for one gene of a human being, close to 150 genes of a microbial gene. So that's telling you that if you have a function that is coming from a human cell, equivalently, you have 150 functions coming from the microbial cell. If you put that in an ecosystem like the human cell lives with the microbial cell, imagine the number of interactions, how much that would be, right? So a bacteria in, in a in a way, they just don't communicate to the human cell. They have other functions. So if you eat food, whatever that food is that could be, also you took a drug for whatever condition you may have that drug or that food, the first barrier they need to cross is the microbial system. Because the microbial system needs to digest that food, needs to convert that drug, for you to be able to benefit from it, or for your cells, human cells, to be able to benefit from it. The bacteria has a system. So if you take a bacteria as a as a system, a bacteria by itself is how we call an antigen, meaning it can also trigger immune response from the human, from the human cell perspective. But the bacteria also has two major functions. It can do what we call it -, anabolism and catabolism, which goes under the metabolism. What does it mean? The anabolism is they produce molecules that your body will not be able to function without them, and they degrade molecules that, if non degraded, they may be toxic to your human cells, right? And that's the metabolism. So bacteria, they produce some vitamins. Now, why do we say a baby should not take any food before the age of six months? Or, I mean, is that what doctors mostly recommend, or why should not take any solid foods? That's the answer. Well, we only give them milk for a simple reason. If we do give a baby a solid food before the age of six months, they get sick, maybe they get constipated, and maybe they have bloating and so on, for a simple reason, they don't have the equipment to degrade that food. If you give them milk, they can degrade it because they have the bacteria called lactobacilli or Bifidobacterium, they're designed to actually degrade milk, right, and to process it for the human to be able to benefit from it. But if you give them plants, they the human body is not equipped to degrade cellulose, which is one of the component of plant cell walls, right only after some time, your body will be able to degrade that cellulose or those plants, because they acquire the bacteria that enables them to do so. So the bacteria is not just a passenger. They're there because there are some functions that the human body cannot perform, from an immune perspective, from metabolism perspective, from producing certain vitamins. But without that, it will not work. Now there are some people come in and say, Ah, of course you're saying, I mean, you because you like microbes, and that's what you're saying. But there are, in some cases, where they're in the in bariatric surgery, we actually cut the colon of some people, they don't have so because the bacteria mostly reside in the colon. If we cut the colon of these people, I mean, they live normally and they have no issue. And some other cases, people say, Listen, Gen3 mice. We've seen some gem3 mics. These mice, they don't have bacteria, and they live like for a year or so. What, what's, what's important to mention here is that maybe they would be able to live without bacteria whatsoever for a year or two. But we don't have substantial longitudinal data saying after 10 years, what would happen to brain function of that person. What would happen to kidney function, what would happen to liver function, and so on so forth. So we cannot say, okay, bacteria, if we remove them, yeah, after you receive nothing today, to my knowledge, there is not a single study showing if you take bacteria completely out of the human, let's say organism, that organism will function properly. The likelihood is no it will not function properly, because bacteria are there for the functions I just mentioned earlier. Okay,
Peter Williams 18:02
so let's talk about where we're moving on today, which is really how stress and I think I'll define stress so psychological, fear, anxiety, you know, cognitive demands, depression, etc, environmental, from a point of view of climatic extremes, I mean really some good stuff on noise, which I'd love to talk about, pathogens, toxicants, pollutants, etc. And then, of course, the physical stresses, which could be lack of exercise and over expenditure of exercise as well, but really circadian rhythm disruption and different dietary approaches, which I probably would love to get onto today on that side. So if we could talk about, if I look at the literature, you know, when I look at it, what's clear is that studies basically show that the more stress you're under, and I think we can say that psychological stress, anxiety, depression and just sort of chronic stress, we definitely see that the gut microbiota will both respond to that and also be influenced from that. So can you expand what you understand with regards to how psychological stressors affect the gut microbiota over time, and then also the other way, how the microbiota may be affecting the stress response as well?
Dr Amine Zorgani 19:34
Excellent question, and it's definitely an emerging field. So as I said, the microbiome produce molecules, and we call them metabolites. In this context, those metabolites travel to different organs, and one of the organs they travel to is the brain, right through the blood brain barrier, right? We call the BBB, right. So they travel from the gut. Towards the brain using a highway called the vagus nerve. If you take a mice I studied on multiple times, but the first ones probably who had really did a great job in it and showing the causality, is a lab of Professor John Cryan from the APC Microbiome Institue, and he's also one of co authors of a very interesting book that Iwould recommend to people to have a look if you're interested into the relation between microbiota and stress. It's called the Psychobiotic Revolution. Yeah, it's a fantastic book. Yeah, exactly. It's a quite a substantial knowledge in there. If you take a mouse and they cut the vagus nerve the mouse doesn't die, but you would see that they change completely their behavior. They become anxious, they want to stay like in a place they don't really like being approached, because there is the highways between the guts and the brain has been disconnected, and we call this the gut brain axis. There are many other accesses, skin access and so forth, but the gut brain axis is the one related to this. Now, there are some studies right showing the causality of the microbiota in initiation stress, mostly done in animals or animal models, mostly mice. In this case, there are many ways how we can do that. Basically, Gem three mice and assessing response to anxiety of that mice and so on so forth. In humans, most of the clinical trials, they're conducted based on a questionnaire basis, right? So we go, for instance, to students in the, let's say, the medicine school and their entry, and then we try to understand their response to stress and the same we collect stool samples to analyze, and then try to do correlation, okay, for a student that was not stressed and the student that was stressed, what was the microbial composition of these guys and how They differ, right? And then we try to build up correlations. And from that, once we find some correlations, we try to identify what microbes are actually mostly dominant or mostly reduced. We try to isolate those microbes, and then we feed, let's say, if we identify the microbe that is enriched in people who do not have stress and depleted in people who do have stress based on the questionnaires. We can then give these microbes to the people that potentially would potentially become stressed and for for whatever reason, and then we can add it in there. Other occasions where this approach is used is for post partum women, pregnant women, there is some occasions where women can become depressed or stressed after the delivery. And this is very important, because it might be trivial or not like not really a big problem. But if you speak to women, pregnant women, who identify it. Some studies have shown that feeding or giving some types of probiotics, not to mention the brand connection whatsoever, to pregnant women before, during and after the delivery, it reduces their stress level, and it gives them a better recovery from that kind of very anxious and tough, tough period. Now all this, it's not the causative effect. I mean, we're seeing Okay, there is a stress. It correlates with certain microbial signatures, right? But how can you eventually make the causation? Okay, if you have this microbes, or you don't have these microbes, you will end up being stressed because subjectively, you're just using questionnaires people, they're saying, I'm anxious or I'm not anxious, right? Another way, which is emerging, but still in its infancy, is using MRI, right? So it's very expensive. That was not many studies have basically used it, taking MRI and really trying to see the response to stress for certain individuals. And it just give us a closer look on how the brain functions in response to stimuli coming from the gut, which is a very promising approach, right? And this is, let's say, starting in the beginning. And, yeah, I hope we see more data on this aspect of really linking the physiology of the brain towards the to the guts. Another unrelated, but let's say unrelated, to the gut, another field called psycho dermatology. We know it's very, very emerging, like it's just it's in the earliest of its s curve, psycho dermatology assess how skin health could influence brain health, right? There are only, let's say, a handful which I could count them on the hand, on the fingers of my hand, reports showing that skin microbiota, this time, not the guts, skin microbiota, can influence through the skin, some stress levels in the brain, but again, still an emerging field, in essence, as well. Isn't
Peter Williams 25:15
Isn't that quite incredible? (amazing, yeah) I mean, because what that tells you is the potential Isn't that quite incredible? (amazing, yeah) I mean, because what that tells you is the potential just complete interconnectedness of everything. And then again, you know, is that skin, as I said to you, if you're just going to live in concrete buildings, you know, how much does that influence? So again, it just develops into the bigger and bigger picture. And you know, if you're not a pet owner, how much does that influence? And you can get this under so and, you know, what are you using on your skin to wash and you know, that sort of stuff. You know, this is certainly, there's, there is quite strong evidence to suggest that maybe we are being overly clean. We are overly washing ourselves. Where is the literature on
Dr Amine Zorgani 25:56
I mean, as I told you, 2% of the food, 2% of the microbes you get is from the food you eat, not like packaged food or packaged goods, it's mostly fruits and vegetables. So if you are washing your fruits and vegetables with soap, don't do that. You're rather eating like detergents than eating anything else. And again, try to favor getting these microbes from, sorry, getting the microbes on the fruits and vegetables. If you go and shop rather go to, you know, markets, rather than supermarkets, where all goods or fruits and vegetables are packaged and probably over, over, sterilized and so on so forth. And as we said, social interaction is also one of very important factor giving you those exchanges. A very, very interesting paper published close to a year ago, one of at least the most extensive ones that looked into social interaction and how the social interaction increased microbial extent between couples, between couples, and then their childrens, and between communities, literally in their neighborhood and so on so forth. And we could see clearly that you don't just exchange, let's say, oral microbiomes, because you're speaking, throwing those microbes in the air, in beadlets of water. You're extending skin microbiota. You're exchanging gut microbiota with your couple with different reasons, and this is the microbial exchange that you need to sustain so and to to be healthy. If we there are some also some reports investigating whether microbial exchange can improve resilience of an ecosystem. What does that? What does that mean, a resilience of an ecosystem. So imagine an ecosystem is basically a family, a father and a mother and some kids, or whatever, parents, two parents and their kids, and maybe they have a dog. That's an ecosystem, if you have a balanced ecosystem, and there is significant or sufficient microbial exchange, healthy one where, let's say you have a parent that is have or has a healthy microbiota -balanced. When I say healthy, doesn't only mean gut, because now and now I know that I will be shut off by many of scientists saying, yeah, come on, we don't yet know what the healthy microbiota is. Of course, we don't know yet because the healthy microbiota of Armine is different than Pete's microbiota and but we're both healthy, right? In that sense, there are two different microbiota that can be defined in a healthy one. One is called an engrafted
Peter Williams 28:42
Go ahead. Can we? Can we go Can we give us an indication, just a rough indication, of what we understand with from a point of view of what is most likely going to be. We can't tell on an individual basis what is a healthy microbiome, but we have some, quite a lot, large amount of data to know that a lot of species with a lot of genetic diversity is indicative of probably a healthy microbiome. So we can't be 100% sure, but we've got some leads, haven't we? Like you know, there are certain we're pretty sure health promoting bacteria like Bifido and lacto would be part of that. And if they're not there, then it's usually, you know, part potentially less healthy microbiome. So can you give us some basic understandings of what the literature is telling us from a point of view of diversity and species numbers, and maybe some of the understanding around let's assume we did a stool sample what we would expect to see in a healthy microbiome, even though we're not 100% sure. Really, what is, you know, we're not, we're not clear, are we? Yeah, we're moving towards a point. But as I said to everyone. Microbiome is probably different because we but we do have some guidelines, don't we, from from a point of view of what we would expect to see currently based off the literature. So could you just expand on some of those basics? Absolutely,
Dr Amine Zorgani 30:14
I think number one is maybe to, let's say clarify the keywords, right, and diversity and composition. So diversity is not the same as the composition. Diversity is like how much different variants of specific species you would have in that same ecosystem, where composition is what type of microbes are basically contributing to that ecosystem or to that organ of microbiota. So if we speak about diversity here, and it's also to be put in a clear context, right, diversity of different microbiota is different, meaning that if you speak about the gut microbiota, the highest the diversity we know is the better. So the more different microbes you have in your guts, is better. We know that people from the hunter gatherer, they have much higher diversity than we do because they just didn't use all the rubbish that we've consumed over the times and the drugs and what's also there. But when we speak about the vaginal microbiota, a higher diversity is completely the opposite of what you want, literally the opposite. Because in so can you, can
Peter Williams 31:32
you expand on that? Because, again, I think this is an incredibly interesting area. It's an area that we've treated consistently for about last 10 years, and it's unbelievably easy on many females that we see who have had bacterial vaginosis, various different inflammatory disorders vaginally. And it's because in almost all cases, the microbiome is abnormal. So can you just explain that area? Again, sorry, I had to but in, but I think again, it's the thing about this is that we have all this literature about this, and we see all these women suffering for years and years and years, and then they're consistently fed with different rounds of antibiotics and antibiotics and antibiotics, which number one, do the job that they need to do, but then several months later, they've actually potentially made the situation worse. Yeah, absolutely.
Dr Amine Zorgani 32:30
So if you speak to me, or you ask me, What's your top priority microbiota, I would say without a doubt, the vagina microbiota, although I don't have a vagina, but I believe it's it's a completely underestimated microbiota for many reasons, because we don't pour a lot of money on this women's health research as well. But let's speak about the science and what science says. Science says that if you take three, 3250 women from one of the biggest studies from the Citizen Science by Professor Sarah Labeer from the Antwerp University, and they called the ISALA Study right? They took these women and they these women, each of them gave a vaginal sample, and they sequenced it and they assess what is the diversity? It confirms all what the the literature says that if you have a woman healthy, you would have the one of the most dominant bacteria is lactobacillus crispatus, which is very much associated with a healthy vaginal microbiota, right when you look into the opposite for disease, women which have BV, or they have infertility issues, or they have tried IVF and vitro fertilization, and it didn't work. Now, reports are emerging showing that if that's the case, you have a very likely an increase of gardnerella vaginalis, one of the pathogens, or opportunistic pathogens. In the case of the vagina, we have five CTS - Community State Types, meaning that we can classify vaginal microbiota based on the bacteria that they have. It that community state type one is dominated by lactobacillus crispatus and jensenii afterwards for two, and so on and so on, so forth. So now it's different
Peter Williams 34:23
because, because lactobacillus is a is a super group of bacteria, and within that there are individual species like lactobacillus crispatus. So saying there is that the community states are usually defined by a dominant lactobacillus species, absolutely
Dr Amine Zorgani 34:43
so not to, not to have to say, confuse that with other lactobacilli that you would find in the gut. Yeah, these are vaginal specific bacteria that you only and mostly found them in the vagina. So now it don't get fooled with, you know, a lot of marketing claims and people saying to you, yeah, take lactobacillus Rhamnosis, which is one of also mostly used probiotic for, you know, gut health and so on. And, yeah, let's just use it for vaginal microbiota. I'm not saying it might not work. It might work, but it's not the inhabitant of the it's like taking an Eskimo and traveling the desert and saying, Yeah, try to cope with that. So you might see results, but it's not the bacteria that is there. So it's very important that to make a difference between a bacteria that is from that organ and a bacteria that's coming completely from another organ. Not saying you would not be able to see results, but it's not designed for that by nature, right? So here, if you would have dysbiosis in the vaginal microbiota, you shift, actually, from a community state type healthy, which is one, two and and to another one which is unhealthy, that is three and four, five is also a healthy one. Yeah, or between. It can shift between healthy to an unhealthy. So reversing that process, it requires implementing a procedure that enables you to actually bring that up, right? One of the procedures that is experimental, and there are different clinical trials on it. It's called vaginal microbial transplantation. There was a very interesting report published in The Lancet with one of the professors that I have interviewed who had the honor to interview in the Microbiome Mavericks podcast, which basically there is women that was having different miscarriages, and she had this successive, repeated bacterial vaginosis. They took another healthy woman, they collected the vaginal fluids from this one, and they did this vaginal microbial transplantation. After five months, the woman became pregnant. By far, I think the vaginal microbiota is the most accessible organ or a component to be able to modify and address most of the issues that women are suffering from, BV as you said, bacterial vaginosis, candidacies and so on so forth, and reduce this and justified, in Some cases, use of antibiotics because solutions can be addressed in this way as well. Yeah. And
Peter Williams 37:24
I think the key thing for lactobacillus, one of its key roles, isn't it, is that it does an amazing job of just reducing the pH (absolutely) and by reducing the pH, that's why it kills a lot of stuff, because most bacteria can't survive in such low states, and that's the beauty of of lactobacillus.
D
And look isn't it crazy? I mean, there's so much literature out on this, and yet we just don't hear that much of it. I mean, we see a we see a lot of women in this situation, and generally, it's such an uncomplicated and easy way to treat
Dr Amine Zorgani 38:02
I mean, you wouldn't be able to believe Pete, how many messages I actually get on, on, on, on LinkedIn, women, really, in some cases, to be honest, like really desperately looking for a solution, and on, in total honesty, The European regulation is not helping either, there was a solution or solutions existing out there with some creams that contains this specific species of lactobacillus crispatus. Unfortunately, the reglamentation had decided that we cannot put a live bacteria anymore into a medical device, in this case, the cream. So all those products were taken out of the market, and I received many messages, women asking me, listen if you want to ask to sign a petition, let's do that, because we need this product to be back on the market.
Peter Williams 38:52
Why do you think that is because, I mean, we've got, we've got, we've got labs that give us the capacity to test for this, for vaginal dysbiosis, really quite cheap to do. And then we've got, as I say, with the some companies who are already doing strain specific bacterial species, Crsipatus being one of the dominant ones in the formulas, and that either taking that orally or they are being advised sometimes to, in some way. Just take it intra vaginally as well. To see, I mean, such a simple strategy. It's, you know, for such a, you know, sometimes, you know, these women have had this for decades, you know,
Dr Amine Zorgani 39:34
so oral supplementation is still not, not an issue whatsoever. So we can definitely take Crispatus or any other strains or species orally. It's rather the vaginal supplementation that is now prohibited with the live bacteria, because we're evolving in a very, let's say, fast growing, emerging field as well. And again, some actors they've seen, okay, there. Is a solution we can bring there. They brought it. However, the regulation still vague. If you speak about probiotics or any biotechs in that matter, the regulation is completely sparse and clear, be it in Europe or in the States, it's same. We now have probiotics as supplements, but we could put many claims or no claims. It depends on which jurisdiction you are. So it's mostly, I think, the how to say the science is moving fast, the commercial aspect is moving faster, while the regulation is not catching up, and they're really behind. So it puts the now, the consumer or the patient, and a very tough position, because the the regulation is really, let's say, 10 years behind to really catch up with how science brought any applications, and then we end up by having this kind of situations, products being put in market. Because, okay, regulation, regulation was not clear, so we could, okay, whatever. Let's just put it because there is science backing it up. Oh, guys, what are you doing? I mean, you should not put it bacteria into a medical device, because in some cases, the people who actually work on this type of regimentation don't know the science behind the microbiota. For them, a medical device is a cream that doesn't have any contamination if you look into Yeah, that's the thing, right? If you put a cream in a vaginal cavity, whatever that is on the surface or in the inside the vagina, you need to show a spotless test that has no contamination, zero, and you are telling me I'm going to put a bacteria on it. Are you crazy? That's how it works. Okay, let's just remove them. But they don't know that this bacteria have a very essential role to actually curing, in this case, really curing, although they stay as a supplement, but really curing diseases like BV in this case, yeah,
Peter Williams 41:56
as I said to you, I'm pretty sure this was going to happen. We go completely off left field, pretty amazing. And, and look, I think what I'm also I'm already looking at time. We're sort of nearly 50 minutes in already, mate. So, so look, here's what I want to do, because I actually given I'm going to have to ask you one again, if that's okay. Because what I would love to talk about, and I think we probably need, because even that, even what we've just talked about the vaginal aspect, you could do a whole podcast on that easily. So what I would like to do a podcast on with you as soon as you can, would be one about really how the microbiome changes with different dietary approaches, and what we've learned from that and the pros and cons as much as possible, but I think we're going to have to leave that for another day. But that's going to be an absolute classic one, because then we get into short term gains for maybe longer, long term fails. You know, what is the macro nutrient proportions? You know, what happens if we have a high protein diet long term, etc? And I would love to get into that one, but I think even just on that subject, we're probably looking at a full podcast on that. So if I can use your expertise and just bring that simply back to what we understand with the growing amount of evidence that looks at how the host microbiome responds to stress, and how that's how stress is either exaggerated or mediated. So how the stress influence the microbiome, and how does the microbiome mediate the stress responses as well? That would be and what are the what are the long term consequences of someone, on the microbiome, but not just the microbiome, maybe the sort of just systemic health of chronic, unrelenting stress, that would be a, probably a really good place to sort of get.
Dr Amine Zorgani 43:59
again, as you said, the excitement bring us all to go off in tangents and deviate from the topic, but you've done a good job bringing it back to the stress. So today, there are two different levels to enable us to study the microbiome, regardless whether that's stress or any other conditions that we might be looking at it number one or number level one of complexity is the composition. So if you are stressed, how would that stress would change the composition of your microbiota, meaning reducing certain microbes that might be beneficial to you and increase in other microbes that might not be beneficial to you? The second layer of complexity is more of a functionality. There are some functions that this microbiota is performing, like, for instance, producing metabolites such as short chain fatty acids or GABA, for instance, which is also known as neurotransmitter, yeah, that can actually either reduce or increase. It's always a chicken and egg relationship. It's a bi directional communication. If you are stressed, that stress, if it take any stressed person, depends on how that person would react, you would find that that stress would always come with either hard or loose stool, and mostly comes with bloating. The Bloating is an immediate result of a fermentation. What does that mean? If you eat any food, the bacteria will ferment that food and produce gas, which gives you that bloating. So the more stressed you are, you would push certain bacteria that increase their fermentation process to increase the production of certain gasses that gives you that kind of bloating and comfort, really, from a digestive perspective. Now, some studies, some done by companies, some done by researchers, have shown that supplementing with specific type of
probiotics, let's say Bifidobacterium, which is one of the most successful ones, and there is the very famous LGG, which called Lactobacillus GG, it's one of the most extensively studied probiotics, and showing that supplementing with probiotics can actually reduce stress in different scenarios, be it in a military settings where you have you know, or for veterans from the military, usually mostly done in states. So increasing the microbial load with this specific probiotics has an influence. But okay, tell me why and how it does it. There are two ways. We call it a bifidogenic effect. What does mean? A Bifido genic effect. So if you bring an ingredient or a supplement, mostly prebiotic or probiotic, let's say, if you're given a probiotic as a Bifidobacterium bifidum as a species, right? BB 15 as a strain that bacteria when it gets to the intestine, it's not just this bacteria by itself, will do the effect of reducing stress by different ways. Remember, stress is not located in the gut. It's actually located in the brain. So first, there are some instances where the bacteria needs to push the ecosystem to produce metabolites, mostly short chain fatty acid and mostly most studied butyrate. That's why you get some health practitioners, although it smells ugly, very bad, they do give butyrate to their patients certain quantities of it, yeah, to enable that butylate to travel from the gut to the blood brain barrier and actually eventually reach the brain. And it shows that reduces the stress. But again, it's not everybody who can take a very bad, smelly butyrate that's why giving this type of prebiotics or probiotics can increase the bifidobacteria. That's we call the Bifido genic effect, which are very good producers of short chain fatty acids. Amongst is butyrate, usually is the most, the highest produced, followed by acetate and propionate as metabolites, which give us that that boost, right. Now there was, again, as I told you, it's so the research is moving so fast that sometimes you cannot even keep up with the changes and the signs that we are acquiring. A very recent study done in the by professor in Germany, Heller, and they actually showed that it's not just about the probiotics that you're giving. They took infants, I think it was up to one a year old. It actually depends on the Circadian rhythm, because they found out that these bacteria actually changes with time. So there is a day time and there is night time where it depends on when you're giving these probiotics or prebiotics, in that case, to these infants, you get a different reaction, because the composition of this microbiota changes in that sense, and this is how, basically, it's very dynamic. Now, if you're speaking about sampling and assessing whether, when are you mostly stressed, you're going to sample the microbiota to assess that stress. It actually also depends on what time of the day, right? You look at yourself and you test yourself end of your weekend, basically the night of Sunday, right? And then you test yourself on Friday, and you measure your stress level, like with the smartwatch, like with the, you know, heartbeats and whatsoever, and then you correlate that stress with the microbiota composition, you would find there is an interesting correlation there, because your stress reduces drastically if you had a good weekend, not like in jobs and traffic, but if you had a good weekend at the end of Sunday, you feel relieved. You. You to relax because you just reduce your stress maximum. Your microbiota gets equilibrated in that sense. But the stress level goes up because of the week if you have a stress life, and then that actually accompanies with the changes in the microbiota. But one very important aspect they want to cover there, and maybe that will be my last word on this one. It's very, very important to know that it's not all the microbiota that will change. It's not like all your microbiota will completely change. There are two types of microbiota in your guts or your skin and whatsoever. One is the engrafted microbiota. Basically, this is like a corn stone. We call them the keystone species. They're there to stay there, right? And if these ones are troubled, you may have disease in issues. And there is one the environmental microbiota that that's the one who actually responded to stress, that response to the food, response to every external stimuli. That's the one which changes. It's it's not bad if it goes down certain species or goes up. It's bad if it becomes chronic, and that's where you get this chronic stress, where it actually goes beyond the environmental microbiota, it gets deeper and started touching the engrafted microbiota. And that are the changes that you cannot usually easily repair, in that sense.
Peter Williams 51:22
So so just on that, are there any so we've got, again, we've got the super kingdoms, haven't we, which we call a phyla and then we've got the species, which would be the sort of lactobacillus species, or the Bifido group, just as an example, in psychological chronic stress. What if we did stool samples on individuals? What would be the bacterial species, species, individual, not individual species, but individual groups that we would expect, maybe to see, they are not the in the levels that we would like to see what we would, what would, what would, what does the literature tell us?
Dr Amine Zorgani 52:05
By far, there is one very it comes always back in the reports. It's also come from a very interesting study done in the University of Ghent in the Flemish Region of Belgium. Yeah. And they said, I think more than a 1800 people in that study, if you're not mistaken. On the numbers, by far, is coprococcus species, or phylum, coprococcus coprae, if I'm not mistaken, the species, and that is actually a bacteria that you don't want to see it low in the case of a healthy human. And whenever we had people with depression or anxiety symptoms, we've seen clear correlation of a reduction of that species and an increase of anxiety and depression, along with other species like Bifidobacterium, that always comes as a as a Bifido genic and as, let's say, as a Bifidobacterium, producers of certain fatty acids and many others. But the science points more towards this specific species as being dominant in a healthy individual without any stress, and it decreases drastically to levels in some cases undetectable. I actually had one, one patient who had post depression from covid and pre diabetes and stopped working, literally. And she had done two different stool samples from two different companies, and both they shared undetectable levels of this same species, which correlates with all the reports I mentioned earlier. So if there is one to mention, that will be the one Rosburia is another one, although the science is not very solid on it. I mean, it depends on how much studies there have been there. Coprococcus is one that is mostly just on
Peter Williams 53:53
Just on Coprococcus, how would you increase its how would you bring back its levels? Then, what would be the intervention that you would look to do,
Dr Amine Zorgani 54:01
if there was the the most straightforward would be probiotic with coprocopus corporate today, that aren't To my knowledge, maybe there are some companies work on it, but you could not find it in the market. Unfortunately, market, no, it's not available, although I do know there are some companies working in the background on it, mostly in the in the Irish parts of the
Peter Williams 54:25
No, I mean, again, this comes back to number one, you've got to deal with what's causing
No, I mean, again, this comes back to number one, you've got to deal with what's causing a problem in the first thing that is, well, what, why are you so stressed, and what can we do? And then I suppose, secondly, you know that it comes back to, for me, it would be, well, how can we increase just food diversity, colors, etc, and absolutely so would doing that aspect and stimulating as much short chain fatty acids as possible have a foot sort of carry out, carry over influence, maybe not just on, on coprococcus, but. Because my understanding is, is that, is it a, is it copracoccus is, is established as a, as a bacteria, from, you know, from from being a toddler, and then it's levels are determined by how you live your life as you go further on from there.
Dr Amine Zorgani 55:20
So when you're at, when you're, let's say, between one to three years, you don't detect the significant levels of copracoccus. Initially we have E coli, and then it changes to Bifidobacterium and lactobacilli, and then with time it comes, I think again, it needs to be substantiated with other studies that would enable us to actually make a judgment whether a dietary supplementation could influence coprococcus. However, there is different ways how we could actually do that. This is, again, a scientific hypothesis, so studies I have read, yeah. Now what we can do is to identify the phenotypes, right? So if you look into a depressed person, just to take an example, which they do have a reduced coproccocus type species, phenotype I mean, maybe this person had a reduction of, let's say, metabolism of x, y sugars and a reduction of anabolism or production of hy vitamins. Restoring those phenotypes by dietary supplementation will be mostly appropriate, because here you're addressing the functions that are missing, not just the bacteria that are missing, restoring a function in some instances, can also lead to a restoration of the bacterial diversity if a bacteria again, to be very clear, if a bacteria is not detected in a microbial test guts, microbial test doesn't mean it's not there. It should also mean that technology was not powerful enough to pick it up. So maybe it's there very low amounts. So just adjusting the dietary will enable you to increase its levels, because it's it's just not unfavorable for that bacteria to be able to sustain and increase its and we've seen data if you have certain low levels of bifido bacterium in in this case, sure it is also the case. Add in specific types of prebiotics. Prebiotics, let's simplify. Is the food of probiotics or the food of the bacteria? In general, if you add a specific type of probiotics, not enerving or false or go some of these are mostly generic prebiotics that you can also use and incorporate them in your food. There are some specific type of prebiotics that are mostly targeting specific type of bacteria. This can also bring it's not this can it does increase the composition of does increase the abundance of those bacteria in there. So dietary supplementation, targeted dietary supplementation, is also a mean to increase the levels of abundance of bacteria. But again, you gotta identify what dietary supplementation you gotta put for what bacteria targeted increase.
Peter Williams 58:14
So, so what you're saying, there, is that it's a bit of hit and miss. If you just go out and get a probiotic, and it's we're learning that we need strain specific probiotics that are justified in science to do a very specific job. And if you don't get those strain specifics from good companies, the risk is that you've just bought a probiotic that just maybe good for many things, but it's not doing the job that you need it to specifically do. And I think that's, I think, probably the key change in in the way we think about, certainly probiotics in the last 10 years, is that you've got to have, you've got to have the electrician to deal with your electrics. You can't bring the plumber. He's a, he's a he's a manual labor, a skilled manual labor, but he's not the one that you need. And I think that's definitely a change. What would be the takeaways? So let's assume that we have a stressed individual, and that stressed individual has digestive complaints that go seem to be linked to the stress, what would be the sort of takeaways that we would need to think about based on your understanding of stress and the microbiome, with regards to what interventions could I put together? Now, obviously, the key thing for me is, well, what's causing the stress? Absolutely, we don't, we don't deal with what's causing the stress. We're gonna always going to have the mechanistic aspect of stress influencing the microbiotica and again, the the flip side to that as well, and particularly, we're talking about chronic, unrelenting stress over long periods of time, which were we'd expect to see the changes in the microbiotic composition, but also the changes at the gut lining, and then the problems with the systemic the systemic risk from there what would be your, what would be your sort of tips on that side.
Dr Amine Zorgani 1:00:16
So the tips will definitely vary on the person, and whether that person is thin or little bit overweight. It depends whether you're What's your type of dietary eating, but if there is a general recommendation that I would do, and whether you're healthy or not, whether you're stressed or not, I would say, try to start experimenting, because it also depends, let's say we are working on a solution in the background that I cannot tell you now, but I hope in the in the coming months, that will eventually solve this kind of issues. As you said, you gotta bring electrician to deal with the electricity here we're trying to also create, is to create a solution that enables me to be everywhere in the world as a scientist, so I don't have to like, when somebody comes to me and say, as the question, you say, it's a person specific. You tell me, me speed, I do x y, x y, and I want to solve x y problem. I know who you are. I know your profile. What's your anthropometric characteristics? Yeah, and I know what the science says. And they connect both and tell you, Okay, you should be, probably be taking these ones. The Science points towards taking this type of probiotic, this type of prebiotic, with this type of dietary supplementation, changing whatsoever, which will enable you to potentially record, okay, that's the science saying it. But I cannot do this for everybody in the world. That's the solution working on to enable this, and I hope it will solve such problem. But there are things that you can definitely do without you waiting for us until then, I would say is number one is try start an incorporating types of prebiotic in your food, right? You can go with a probiotic, but they would say, first, start with a prebiotic. There are some which aren't really that expensive that you can really use them on a daily basis, and it will honestly show you some increased resilience in that sense, yeah, like, there are some yeast, like, extracts that you can have. You can add them to your food. There are some types of prebiotics that you can actually start using, like inulin phos and goes and so on, so forth. And then you assess with your body, how your body is reacting to that, and how you're doing with it. That's not expensive things that you can actually use, but incorporating more fruits and ligands into your food depends if you have ideas or not, so you have to consult with your doctor in that sense as well. But when it comes to probiotics, you cannot just go and buy a probiotic because it was labeled on it good for stress or mood improvement and whatsoever. You gotta understand why you're buying it, because it's not a cheaper product, and for how long you should be using it, and what should be expecting from it. And that's all depends on explicitly, on a person per person condition, because exactly so it just not something we can generalize. Give you a general, general recommendation, yeah, let's just take this one. It's my work. No, if you take it a bifid bacterium and fantas which is isolated from infants, and you give it to an adult, don't expect that other to be like an infant mood, because it works like that. It's just not different ecosystem. And infant has a bacteria that is there. It stays for a bit, and then it actually goes away, because it does have a function, right?
Peter Williams 1:03:52
So what I love about what you're saying here is that regardless of the condition, so it's stress, you have to understand the ecosystem that an individual body is living in, you've got to understand the context of what's going on because, and regardless of whether you choose the appropriate probiotics or prebiotics, if the mechanisms that are consistently driving the stress response are still going on are even worse, then it's unlikely you're going to see any results, even though the probiotics may be doing a really good job. So I'm assuming that's what you're trying to expand, expand,
Dr Amine Zorgani 1:04:30
I mean to to really explain it in a very simple ways. For will it say, for a probiotic is scientifically proven to do have an effect on stress that is brought to market because of those claims that probiotic scientifically means that same bacteria, or probiotic was tested in a clinical setting. Right when you test a bacteria in a clinical setting, you have, or in a clinical study, you have what we call an inclusion and an exclusion criteria. You. Meaning that the people who were tested, they needed to be having specific criteria and not having specific criteria. So if you're taking that probiotic, you gotta imagine yourself within those inclusion and exclusion criteria. If you're not it, the likelihood of that thing to work is it's lower or lower, it might work. It doesn't mean it would not. And this is the real thing.
Peter Williams 1:05:24
This is the real tricky gold dust aspect of of being, you know, great clinicians. Great clinicians have to basically try and modulate this, the understanding and the story and what the potential outcomes are going to be for the patient, whilst trying to positively psychologically say, yeah, we can do things about this, but you've got to tell a story in the way that you're not suggesting that this probiotic is going to solve it, but you're not suggesting it may not be helpful. And I think this is, I think this is always the trouble the always the trouble is that is that, as you said to you, is that when you're looking at a strain specific for a specific job, you exactly what you've just said. It's shown that it works in this particular environment or process, but it may not work in something else. And I think absolutely, and I get it from patients. You know, patients are they're not well. They're looking for results, and unfortunately, you have to be right. Look, they may work. It's worth giving it a go. We think we've got the context. It's worth giving us a go. It's really sort of, it's tricky as a clinician, trying to, trying to keep patients on a positive psychological pathway without saying that. You know, this thing will will solve it or it might not do, but it's worth a shot. So that's the difficulty, and the difficulty isn't it is that that probiotic maybe do actually have done a really spectacular job. It's done the job that you need it to do, but all the other aspects haven't been dealt with, so you don't really see any changes or any results, even though that that's done the job that you needed it to do absolutely.
Dr Amine Zorgani 1:07:03
And again, it's a context specific, right? So what happens is that there are, I said, just not this is a very underestimated number, 100,000 different brands of probiotics out there. And facing to that, there are 3725 clinical trials on the word probiotic and clinical trial.gov that show that so how any scientist or any clinician or any human being in that matter would be able to say what probiotic in this 100 brands in what clinical studies and which one I should be Taking? Yeah, human brain cannot do that. A solution we're working on. I hope we will be able to do that. You can't.
Peter Williams 1:07:45
I mean, I mean, you can give them a best guesstimate,
Dr Amine Zorgani 1:07:49
exactly, just what you do. It's exactly so now it's an estimation. And the likelihood of that work because of experience, because of, you know, a lot of strains we dealt with, worked with and so on. There is a difference between, you see, it's in a probiotic in a bottle only actually works on that probiotic in a lab. And you know what that bacteria looks like, and what does it do? Why it doesn't do what it doesn't do. So that's the difference we have. We have an insider look that enables you to actually, okay, it actually, there is a likelihood, from a mechanism of action perspective, for that to work in this specific context, not in another one, yeah, but more to come. And I hope,
Peter Williams 1:08:31
yeah, look, I would like will keep up to again your your wealth and knowledge in this area is just outstanding. It's fantastic talking to you on this. I would love to do how the microbiome is influenced by diet, but importantly, different dietary approaches, because in clinic, one of the difficulties, real difficult aspects that we have is that you're using a dietary approach for a certain outcome over a certain period of time, and once you've gone past that time frame, that dietary output may be having a more systemic effect negatively, particularly on the microbiome, and we see that time and time and time again. And I would love to dig in with that, with you, to sort of expand that situation. And if we could do that next time, that would be awesome. Absolutely Real pleasure. Thank you so much for your time. I really appreciate it. And all the listeners. Your podcast was the most downloaded podcast of last year, from our from our blog. So great to hear. Hopefully we're gonna, we're gonna keep this going, with regards to because it's just such an amazing and interesting area. Really appreciate it. Al right pal, Thanks. very much. Thanks
Dr Amine Zorgani 1:09:46 for having me. Pete.
