Everything You Didn't Know About the Microbiome

In this episode, I am very privileged to have the opportunity to speak with one of Europe's most forward thinking Microbiome Scientists, Dr Amine Zorgani. 

Dr Zorgani, who refers to himself as a "microbiome maestro"  has over a decade of experience in microbiome research and development and is passionate about furthering the understanding of the role that the microbiome plays in overall health.  In his own words, he is "on a mission to prevent the extinction of the human microbiome" 

During this podcast episode, Amine and myself have an updated conversation about the importance of how the bacteria we carry and come into contact with on a daily basis affects our health. We explore the basic facts around the gut microbiome and expand to lesser known areas such as the skin microbiome. This is a really exciting area and I'm sure you will enjoy this fascinating conversation. 

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Transcript

Peter Williams: 0:00

Go. And we're recording. So welcome to this new episode of functional medicine bitesized, sorry. So usually, as you know, I'm interviewing people that I've spent a lot of time working with or look up to or like what they're doing. And we are going to be speaking to Dr. Amine, Zorgani. Today. Now we're we've only just really met Amin, haven't we sort of been LinkedIn buddies, because we both have a strong interest in the microbiome, which is sort of what the what the podcast is about today. So good afternoon, and thanks for taking the podcast call.

Dr Amine Zorgani: 0:44

Good afternoon, Peter. And thank you for having me.

Peter Williams: 0:46

No problem. It's a pretty significant academic background, yours. So I'm just going to give a brief readout and then I'd really like you to give us the background sort of three or four minutes of how you've ended up what you're doing. And I apologise, we've got some, as much as you want to get rid of the background noise, we've got the kids playing in the school ground, and I can't really dampen it out. So. So a couple of degrees in mathematical science, you've got two master's degrees in microbiology and biotech. You've got a PhD in life sciences and molecular microbiology. You were the former editor of frontiers journal, love that journal. And currently, we've got 15 Peer Reviewed papers, which is around structural bio bioinformatics and molecular biology and microbiology. Is that about right. Got it. All right. (Got it, exactly). I'm more interested in the fact that you're a marathon runner and 2x time karate champion, which is a man after my own heart on that one. So mate, thanks so much for doing the call. As I said, you know, I've enjoyed our interactions on LinkedIn, we seem to be on a similar page. But obviously, you seem to be, you know, this is your area, about the microbiome and where we are with bacteria. So I'd love to, I'd love to hear sort of, you know, how you've got to where you've got to know.

Dr Amine Zorgani: 2:16

Thank you , thank you so much, Pete. And thanks for the lovely introduction. Let's say you've mentioned the karate and the marathon, I would definitely love to go back to that I've kind of missed it a little bit, actually switch to other other discipline, swimming and treadmill at home, simply because I as you you too. I have kids and you know, spending three hours at the gym for karate wasn't an option these days. But I've got my tricks. No, no, my story with with the microbiome, I would say, I will tell you why I was interested in the microbiome was not not something I wanted to do from the beginning. But something a, my ex boss led me to it. And I will tell you that about a little bit. But my background is really is like I started doing microbiology, I think 2005 really, that's a long time ago. But it was my job that was really trying to as an engineer, because I'm an engineer by training, trying to understand how can we manufacture bacteria in a fermenter, a fermenter, or a reactor that's literally like how to call like a huge kind of container where we can control the temperature, we can control the pH we can control the oxygen that goes into it to produce bacteria into high quantities. And during fermentation similar as you can do it at home, you can do it on an industrial scale. But to do that, there is some engineering that you need to do some mathematical kind of equations that you need to solve how to take it from one litre broth fermentation to 1000 litre fermentation. That is the engineering part. And that was literally the thing that I started with when I was you know, in my early career as an engineer, and afterwards, I moved to France where I did a master's degree- that was literally the first steps where I wanted to apply microbiology. And from that perspective, I basically were trying to do with one is also my mentor actually mentioned 15 paper it, it's 16 now because two weeks ago, we've published a paper together with my mentor with whom I started working like 12 years ago. Our job there was basically to understand how bacteria can stick to meet matrixes for instance, when you have people eating, let's say meat or raw meat or not very much cooked meat. They could have some bacteria mainly Escherichia coli, for instance and stick into that meat and cause a new kind of a lot of hemorrhagic infections and so on. And our job was how to understand how these bacteria stick into manage kind of find some proteins of this bacteria that allows the bacteria to stick to the meat and so on. And the bioinformatics part of this work was to kind of put 3D structures of these proteins to understand how they behave, or they're resistant to temperature or to salt or so on, because meat is usually in this kind of refrigerated environments, how bacteria or those proteins react to refrigerated environments. I afterwards went to do a PhD. And this PhD, I was one of the first ones basically working on what we call today, the small non coding RNAs. So you have the DNA, same as humans, bacteria, they do have DNA from the DNA, you get the RNA, which is the second step. And then from the RNA, you get the protein, I was working on the RNA level, literally what we call now, SARS, COVID, or we have this RNA messenger with the moderna vaccine. And so it's same principle our job was basically to understand how small RNAs can give resistance of antibiotic to some of these bacteria. So one of them was streptococcus agalactiae, knowing that streptococcus agalactiae is a bacteria that cause neonatal infection. In France, for instance, you have one death over 1000, every month, right? So there is a lot of babies dying due to these infections. And the bacteria is highly resistant to antibiotic. So my job was basically to find a tool, molecular tool designed to kill this bacteria. Until the second month of my PhD, my ex boss of PhD came to me with a very thick book, and he throws it on my desk, and the book read probiotics and prebiotics. So I looked at him as like, what is this? He said yeah, this is the future of health and medicine, and you have to read it or master it as he said, it's like, okay, but no, this is, you know, what is this, like, I it's not what I'm doing in my PhD. So he left and left the book on my desk. So I opened the book, and it looked at probiotics, and there is microbiome and like, this is literally putting bacteria on people or in people. But I was doing the opposite of that, or just trying to kill bacteria. So it kind of, you know, started tricking to my mouth, like, Okay, that's interesting. So we could literally that's 2011 or 12. That is the moment where I really got into this and started digging deeper and deeper into the microbiome science, how it affects health. And this is common knowledge of people saying microbes are bad, let's kill them all. And you quickly notice that it's not the case that a lot of bacteria, the microbiome is this collective micro organisms, it could be bacteria, fungi, or viruses that lives on us or around us or in us in the gut. And there is there is the first time, let's say, when I really got very hooked into it until today, where it became my mission, understanding how we could modulate the microbiome collectively, not just the guts. Speaking about skin microbiome, oral or vaginal or holobiant as a topic, which we could talk about later. There is the well, can we talk?

Peter Williams: 7:59

Can we talk about that now? Because I always if I'm speaking sometimes, I always define humans as Holobiants? And could you just sort of dig into really the sort of the simple concepts of who we are, if you like, because we're not just what we think we are.

Dr Amine Zorgani: 8:18

No, I totally agree with you, we definitely aren't humans, actually. I mean, you would listen to I will just name some few people on some q, key opinion leaders in the field, ???? is a key opinion leader in from France or John Cryan, or Martin Blaser from the US. They all tell you, you are more a microbe than you are human. So simply because when we look into the number of or the quantity of bacteria in the gut microbiome, we are around one to two pounds, bacteria, right? So that's a lot of microbes you have in there. And if you look into the overall picture we are around there are different numbers, but at least 90% bacteria and 10% human cells so we are outnumbered by bacteria that is not just on the gut that is on the skin. So our skin has this outer layer of bacteria that protects us from UV protects us from pollution from infection, when you get an infection from let's say, Staphylococcus aureus on your skin, you would have some skin key bacteria would fight off that that kind of infection. And a lot of studies, not just one Several studies have shown that when you look into human skin as an example, it's one of my area of expertise. There is an very clear correlation between the disappearance of some or the reduction of some key microbes on the skin and a rise of some key diseases, let's say psoriasis or atopic dermatitis and so on so forth. So there is this is the picture of the holobiant but it doesn't stop on the human being. It goes beyond humans, namely, looking into soil microbiome, where we know that some microbes are key for methane for instance, metabolism, or capturing the co2 from the air, there are some microbes that basically allow plants to grow and metabolise certain minerals, we look into animals, animals, some study shows that some gut, gut bacteria in the animals are quite similar profiles to humans as well, if you have a pet at home, and this pet is interacting with you, without knowing you're actually transmitting some bacteria to them, and vice versa. There are some very recent paper, I think, two months ago was published in Nature, showcasing how we exchange microbes in a couple in a community, with our pets with our environment, and so on. That is even what we call today. Your cloud microbiome is literally you're emitting microbes constantly around you. And that can be used to identify who you are or where you've been as well. So it doesn't stop. I just want to people to understand microbes and holobiant as we know it, it doesn't stop at you, as a human being it goes beyond you. And there is this constant interaction with our environment, given microbes or take microbes from that sometimes can be beneficial sometimes cannot. But that's the collective picture of the holobiant.

Peter Williams: 11:31

So in many ways, this is where you, you need to pick your healthy friends, pick your healthy dog, get out in nature a little bit more. Because, you know, I actually remember the well as you know, there are several papers with regards to, athlete's seem to have a more beneficial microbiome. And I suppose partly because, you know, of physical activity, there's nothing that can't do, but also generally they're exercising outside, I think, as a component of, you know, we're even exploring the gut muscle axis, you know, how are these bacteria influencing the our capacity to to build muscle? Can you expand a little bit more on this, then just on sort of what what are the some of the key concepts that you think and I want to use your title because this is on your LinkedIn Tag, you're on a mission to save the microbiome? Because do you feel as though it's disappearing and disappearing quite quite quickly? And can you talk about where you think it might be disappearing, from a point of view of an individual level to maybe a sort of planetary level?

Dr Amine Zorgani: 12:41

Now, you mentioned something very interesting. This is again, indeed it is on my tagline. That is I am on a mission to save the human microbiome from extension simply is not just my own belief. It is a collective belief where I go community of scientists, there is the this movie that is appeared recently, it's called the invisible extension by Martin Blaser, where, oh, he who is also the author of The Missing Microbes, okay. We know today, for fact, this is not theory, it is fact that the microbiome handed years ago from some individuals, it is different the diversity of at my gut, I'm speaking about the gut here. It is the diversity it is quite different of what we know today. So we also know that when we look into the studies of gut microbiome in general, we would go taken there are several studies that have compared the gut microbiome of tribes like the hunter gatherers, for instance, in and the industrialised microbiome, and you can see a clear separation between these two populations, the gut microbiome of hunter gatherers is quite diverse, whilst the gut microbiome of industrialised population is less diverse. Why that we ask the question, why there is this such a diversity? Number one, the diet, so hunter gatherers, and they don't eat that much of processed food, you know, filled of, you know, nasty stuff in general, but doesn't mean that all processed food is bad, but some of it is actually bad. If you take too many of it. I mean, I don't know, if you take a pack of whatever sweeteners every day, that might actually harm your gut microbiome. The other thing that they don't use a lot of medication, let's say they don't have access to it. Here I name explicitly, antibiotics. Antibiotics are known to be this atomic bomb in the gut where they cannot don't select really, but I have to be cautious here at saying that antibiotics, they've kind of changed the humanity and saved a lot of people doesn't mean they're bad. You're just taking them with no respect to wherever they're meant to be. There taking antibiotics in cold is not good. It's and

Peter Williams: 15:02

I totally agree with you with that I think antibiotics fundamentally are a lifesaver in many aspects of health. Where I think it's still incredibly disappointing is, you know, you're given an antibiotic for quite a serious condition, and it does an amazing job. But there's no thought process going on about well, where does that microbiome get left, you know, a week after a month after a year after? And that's where I think it's disappointing that it's pretty obvious that you know, and I can remember reading studies that were shown in it, the microbiome, from one from one antibiotic treatment can be disturbed for up to a couple of years. So surely you would want to be running some kind of strategy alongside that, that is just trying to help the microbiome because all you're doing is you're you're solving one issue might be really important, and life saving, but you're potentially building issues for later down the line. And I don't get what, I mean, I don't get it, the science is there to to help that. Keep going Amine, this is just a brilliant.

Dr Amine Zorgani: 16:07

No, I totally agree with you. And I think it is very important to our listeners that follow the advice of your doctor. So for two reasons. If a doctor give you antibiotics for let's say, seven days, please don't stop at six, right? Because if you stop at six, you might give chance to some gut bacteria to become resistant to antibiotics, removing your chance from getting actually healed with those antibiotics in the future if you get another infection. So that's number one. Number two, don't take antibiotics by yourself. So okay, I didn't finish the bottle. I'm just going to take more this time, because they just got the same condition, I think. So don't do that, because that's not good. And number three, if your doctor gave you antibiotics, ask them, okay, how this is actually affecting my gut. And what do you propose, as you said to me, for me to kind of heal that we are so fortunate as human beings that our gut can have a little bit resilience. So some studies actually showed that the gut bacteria get back to normal level for you know, more or less healthy people after antibiotic treatment. If the antibiotic treatment is not, let's say, disastrous, because there are some antibiotics where you know, it's very difficult to get back from it, so you need to take care of it afterwards. So this is about antibiotics. This is in the case of the gut. But speaking about the skin, for instance, we are as a human being exposed to an unlimited amount of pollution. There are several studies that shows pollution, environmental pollution, impacts negatively the diversity of skin microbiome, there was a study performed by researchers in France, for instance, where they looked into two major cities in China, one of them was highly polluted, and the other one was not that much polluted. And you could see that some key microbes on the skin, for instance, the diversity of them started going down, namely cutibacterium acnes, one of one of the major, let's say, skin bacteria colonisers or staphylococcus epidermidis, which also went down. That is another very interesting case study with policeman's who, you know, Police Traffic people, basically, they also saw that these guys, their skin microbiome is is destroyed like the almost like they lost complete diversity. Because these people they're all day in sun and they get all the pollution on their faces and so on. Which obviously gave them some issues afterwards. And there is another one and very interesting case study. This one was one man. I think it was from the United Kingdom or from the UK. So he was a truck driver. I think his name was William McCarthy if I remember, I think it was in 2012 shown in The Guardian and other journals. So these girls basically drive in his truck one way in the morning, so get in the sun and just one side of his his face. And when he drives back in the evening is the other side but it's already nighttime so he would not get the the other side exposed. And when you look into his picture, you wouldn't believe it. You wouldn't believe it. His face is literally like separated into one side normal. The other side full of wrinkles like it's unbelievable. It looks like this image was photoshopped. But this guy actually received a tremendous amount of sun exposure UV exposure on one side but not the other. Knowing that some key bacteria on the skin, cutebacterium acnes for instance, produce some high antioxidants on the skin and promote the antioxidant potential of the skin, fighting UV radiation and reducing wrinkles. His face completely lost that right and became very sensitive to UV radiation and so on. This is to say, like all these collectively- processed food, pollution, antibiotics and so on, they're contributing to lowering the diversity of our microbiomes. And hence increasing the loss of it. And obviously leading to next to its extinction. So if we do nothing, today, we will lose that. And there is a very, very important reason why we should do something about it. And I think we will get into it later. There are a new, or very recent approvals of microbiome based therapies based on donors. So people they give their stool, healthy people, they give their stool to treat other people's conditions. And imagine that these healthy people, that these good microbes they have go extinct, how are we going to do tomorrow to take healthy people to treat some people who are deceased? I think that we need to think about it today. And before it's too late, and as a scientist, I believe it is my duty to do something about it for anyway, or anyhow, I could do.

Peter Williams: 21:15

mate fantastic. Can we can we keep on with the skin? Because I know, I know. You're Director of Research and Development for a biotech company in Belgium. I also know that you guys are at the forefront of the skin microbiome revolution, if you like, and I know you're producing probiotics for treatment of acne. I'm very much interested in in going to talk about it, you're you're actually looking at probiotics for skin ageing and skin damage, which is absolutely for me, given that I've had some gene variants looked at with regards to early wrinkling is definitely me. And I love the sun. Definitely me. So let's Can we can we go through those? Because I think is this is the key thing, isn't it? Is that you're looking at these really small ecosystems that just are almost the crux of everything else. So can we talk about some of the work that you're doing on that?

Dr Amine Zorgani: 22:21

Yeah, no, totally. So the skin of microbiome, I think anybody working on this came microbiome are very fortunate compared to the gut, simply because the skin microbiome, let's say the number of species on the skin were around 100 100ish, right? Where in the gut, were looking at 1000 plus species. Not strange. I'm speaking from species perspective. And obviously, another one, which is also the skin is, you know, your outer layer. So you just take a swab, swab your skin, and here you already have a sample of bacteria that has resided on skin. So there is, let's say,

Peter Williams: 23:00

Is that being done now, then? Is that the way you're is? Are the skin microbiome tests?

Dr Amine Zorgani: 23:05

So definitely, there are at least three which I know of, there are skin microbiome tests, it's a new

Peter Williams: 23:09

Which is pretty incredible, isn't it that we're revolution, right? So probably there are three that I know of companies that are on the market, probably less than three to four months, right? So what they do. So simply as the same as you would analyse the gut microbiome for the gut microbiome, how we do it, we take stool samples, right. And then we send those samples for processing. So we remove all sorry, the shit, and we just keep the bacteria. And then we sequence the bacteria. So we look into the DNA of those bacteria who they are and how many there are. Same we do for the skin for the skin is much easier because we just take a swab, and we swab the skin specific area could be the forehead could be the you know, the cheek or whatever, or the nose pocket simply for those who smoke, for instance. And then we could do the same process, we extract the DNA of this bacteria and do sequencing to analyse the population. And that is literally this all advancement only became possible with next generation sequencing. So today, instead of sending your samples like across the world, and paying 1000 or even 10,000 euros for sequencing a bacteria, you could have a little device, right? It's the size of a phone in your lab, and you could sequence in the same day. So that is the advancement of technology that allows us today to actually go quickly from understanding correlation, okay, I'm sick because my bacteria went away or I am sick because this specific bacteria is missing. And that's what we do in the skin microbiome. So there are different approaches. The approach we do is simple. We go into the literature, understand if there are any correlations just give you an example acne, we found that is a correlation because between the inception of acne, and the presence of some scooty bacterium agonists on the skin, so, there is over population of them. So, simply could the bacterium agonists, they love sebum, that is like their fruits and vegetables right. So the main they see that they start over eating on that say they proliferate and they give you this inflammation or they call the lesions. So you get inflamed lesion or non inflamed lesion in the case of acne. Our job was actually to distinguish from the good and the bad. So could you bacterium agonists, as I said, it is 90% of the skin microbiota, like literally is taking the whole space, there are other microbes there. But could you imagine Agnes is one of the key leaders. So what we wanted to do here is trying to understand, are there any or all kuti bacterium Agnes bad? Or are there some of them who can actually be good to the point, they could even fight acne? That's exactly what we did. So we identified within the population of the cutebacterium acnes, who are the bad ones, and who are the good ones, so we focused on the good ones and we'll find from analysing this bacteria, this cutebacterium looking at strain specifics for specific jobs these days, which acnes, they they, they don't produce some key enzymes that will allow the other ones to digest the sebum, hence, removing their food, they die off, and then the acne goes away. Right. So it is kind of a competition. So you would put a bad one with a good one, and then let them compete with each other. If one overtake the other one, obviously, you get the disease gone. And there is a struggle with doing so. It's not like standardised probiotics, really here is a probiotic, or bacteria was isolated from a healthy volunteer. So we take people that are healthy, we take swab, we isolate the bacteria, so we put it back there on a plate and then we isolate it, we characterise it, once we characterise okay, we know exactly what this bacteria do and how it does it. And then we produce it. A nd there is a complete different topic. Because here, we're not researching, we are developing something, right. So we are trying to make a product out of it, which basically you have a bacteria you cannot see with your eye until you can actually touch it with your hands as a powder. And then you need to put it into a cosmetic formulation that someone can use it. And we actually went from identifying a bacteria from someone to actually make it in a product that is usually now sold in market and being used for skin diseases. Mainly acne in this case. I think is, you know, where I think we are going certainly with the probiotics side. And can you talk about I know that there was a 2019 paper in microbiome, where you where you guys talked about skin microbiome transplantation? Can you sort of extrapolate on that a little bit?

Dr Amine Zorgani: 28:11

Yeah, those are the, let's say, one of the earliest, the earliest research we've done. We're actually, in the same time doing the same research as another colleague and his name. He's also known as Dr. armpits. And he's basically he's, yeah, I mean, the name is provocative, right. He basically also took bacteria from the armpit. And we know that some people for instance, they, they smell quite a lot right from the armpit. And what he found that there are some people who doesn't smell. So obvious question, why? Why do some people smell and the other ones don't smell? And one of the reasons is because they have different armpit microbiota. So transplanting some armpit microbiota from people who doesn't smell to some people who do smell, proven to be effective to reducing the smell of those who do smell. And smilarly would have done is also transferring skin bacteria using skin swabs as well, from one person who's healthy to another person who have acne and seeing if that could also reduce acne, for instance, as an example, as well to just it's it was a proof of concept. Can we actually transmit bacteria from one person to another using skin swabs and it proved to be effective. In the paper, you mentioned that there was that one of the let's say, the proof of concept that you can actually, today, transfer bacteria from one to another. However, this is a new thing in the skin microbiome, but it's definitely not a new thing in the case of the gut microbiome show because in the gut microbiome there was probably from the Chinese century. Where were they they call this yellow soup. So people that were like sick they have this, remember was like diarrhoea so on, and they will try to give them some faecal samples as well, and to treat the sickness. But today we talked about more of FMT faecal microbiota transplantation. And there is another area of research, which is way more advanced and compared to the skin microbiome today. Skin microbiome today is mainly there is no company is actually actively working on skin microbiota. Transplantation is more of modulating the skin microbiome using live bacteria, or probiotics, or prebiotics, for some people, postbiotics is for the people to know is what the bacteria actually produced. Right?

Peter Williams: 30:51

And can you talk about that a little bit more, because that is sort of we're in the world where we have prebiotics, probiotics, and post biotics, which is sort of their new newer side that we're learning with regards to the bacteria, creating new molecules, new short chain fatty acids that actually seem to then leave the gut and go all the way

Dr Amine Zorgani: 31:09

No, totally 100% agree with you. So I mean, around the body and do really good stuff. And this is always the conversation. This is what's really interesting about this conversation, while I'm absolutely loving this is that, you know, the way we treat people in clinic, is that most of the people who come to see us are coming to see us because they've been sick for a very long time. They've gone through traditional methods of conventional medicine. And it's been exhausted. And I think simply because, and they've done some, you know, some fantastic interventions, all the right sort of, you know, testing, etc. People are still sick. And I think it's fundamentally because they don't ask the question first, that we're actually more bacteria than human cells. So maybe actually it is our bacteria that we've got to that is the saying you are what you eat, right? So whatever you concentrate on at least 50% of the picture has to be that. And yet, they don't go there, which I find still quite incredible given on the speed of what we're learning the speed of, you know, we live, they are us and we are them. And if they're not in great shape, then we're not in great shape. So can you maybe talk about that because if I take you back to what you talked about those nomadic tribes, one of the key things in that is fibre. So your thoughts on on fibre because you know, we're in this weird and wonderful about have this diet, have that diet have that diet? But if we were talking about what should we be giving our microbiome so that it can do the best job it needs to do for you? What would be your opinion there?

Peter Williams: 32:43

Yeah, absolutely mate. Yeah, yeah.

Dr Amine Zorgani: 32:46

So the prebiotic is the food of bacteria. As you've said, fibre, for instance, is one of them. put in your tummy, it is what you're going to get afterwards. Sebum is one of them for those who lives on the skin, and so You've mentioned as well, I would like to go back into this on, so forth. So literally, the prebiotic is what the bacteria prebiotic probiotic and postbiotic, maybe just a very have as a breakfast, dinner and brunch. The probiotic is the small definition. bacteria themselves. The most updated definition of probiotics is live bacteria that would have a positive effect on the host, which is the human or the plant and so on, because there are probiotics for fish or for dogs and so on. So it needs to have needs to be live and needs to have a specific or at least measurable positive effects. Okay. The post biotic is what you've mentioned, is what this bacteria produce short chain fatty acids, some of them actually produce vitamins. And they produce, you know, things that will enable us to kind of function properly. If we, if we look into the gut microbiome, for instance, so these bacteria are swimming into our intestine, you know, freely happy. They're stuck sometimes to the mucus of our intestine as well. But for these bacteria to stay alive, to keep doing what they're doing, producing these short chain fatty acids, namely butyrate or acetate or even propionate. Butyrate for instance is known to keep the gut lining intact. It is known to be a molecule that enables some people even show that there is a communication between the gut and the brain to the vagul nerve and this improves our mental health. These bacteria to became and to stay functional, they need food, one of the food that the bacteria like is fibre. So and then diversification of fibre. Why? Because you have in your gut, for instance, 1000 species plus and trillions and trillions of bacteria from different strains and so on. If you always eat the same fibre, they would not, they would lose some diversification because you would have some bacteria actually became more prominent. And that is very interesting, a lot of interesting examples, where some populations started eating seaweed, and I think in Japan, and you would see them, their gut microbiota is more adapted to that. But if you take it today, and we put you in Japan, you start eating like Japanese food and seaweed, and so on your gut microbiota will be shaped. And I need people to stop for one second, think about what I'm going to say, nature, produce food in seasons, right? We don't get, you know, food all at once. We get specific vegetables and fruit in different seasons, for a specific reason to give us this diversity that nature is, you know, freely helping us guys, this is what I'm giving you in winter, this is what I'm giving you in summer, this one I'm giving you in spring, this one in autumn. So if you follow the seasons, while you eat fruits and vegetables that can give you the diversity you would like to get. Another thing, there was even an article published in the Guardian. A lot of scientists spoke in there about the necessity of eating at least 30 fruits and vegetables per month. Right. So the more you diversify the input of fibres, the better the results will become from increasing your diversity of the gut. This is just for the gut. So people say okay, diversity in the gut, the more diverse the better. And we know that, but diversity is not always the right way. For other microbiomes. I would like to name here, the vaginal microbiome. So the vaginal microbiome, the diversity is not good. Because the vaginal microbiome is more very less diverse, we have more one of dominant bacteria, like Turkish for instance is more dominant in there. And for that there is other things that you can do to improve for women, for instance, vaginal health, but for the gut to come back to that improving or increasing the fibre intake or the diversification as well not like eat anything that has fibre will enable you to improve the diversity. Another thing that I would like to add and this is a study that was published recently by the couple Sonnenberg, Justin Sonnenberg and his wife, their researchers from Stanford University, extensively studying the influence of diet on the gut microbiome, and they mentioned something thats quite interesting. They did two things, fermented food and high fibre rich diets. And they look into the impact of these two on the gut microbiome composition. And they found that fermented foods, for instance, was more or was better at improving gut diversity than fibre for the people who already had a less diverse gut microbiome. So if your gut microbiome is already less diverse, fermented foods work better. For the simple reason fermented foods contain natural probiotics. Yeah, right. Because putting probiotics in the gods also improve that. There are different ways how you can do that fermented food is one of them. And don't go and buy pickles that are on the shelf, you know, non refrigerated because those aren't fermented. The ones that are fermented, you will always find them into four degrees, because bacteria, they're sensitive to temperature and they will die. So you want to get something that is cold, or at least preserved in a colder environment. And that is the fermented food, so diet very good. Probiotics can improve fermented food also adds into that diversity.

Peter Williams: 39:12

here's I tried to explain and I might be wrong with this. Obviously, you being the expert can either say no, that's rubbish and redefine it. But probiotics don't repopulate our microbiome. They sort of act like policemen for a period of time, whilst hopefully your microbiome can get on its own two feet dependent on how well it's doing what you're feeding your own microbiome with. And then you sort of pooped the probiotics out, you know, seven to 10 days up to 14 days. Is that still is that is that correct?

Dr Amine Zorgani: 39:51

So you've asked the million dollar question right? And I would I wouldn't take the Joker here. But I would say the jury's still out. All right. So we do know that taking probiotics after 48 hours, they already transit your intestine. And some of them actually colonise a little bit, but some of them don't. But it is very hard to know exactly where they do that and how they do it simply because we don't have the means, technological means that allows us to do that. Not yet. There are some people working on it, but not yet. However, I think because this is the question is people say, do actually probiotic work, do they really do something? Or yeah, it is just okay, this new trend of taking probiotics to you know, whatever. So, my answer is simple. Probiotic works if you actually need them. So if you're healthy and you're you know, you have let's say, you have a nice stool and nothing is issue with you. You're you know, you practice sports, you exercise, you eat diverse and so on, probably probiotic will do nothing, right. So don't probably don't bother with that. If you're already taking some fermented food, yoghurt, and, you know, sauerkraut or other stuff. Yeah, maybe stick to that. And I don't think probiotic will make you a lot of change. However, for some people who were actually that are suffering from chronic diseases where we know that some key bacteria they're missing. I've just to give you one case study. One day, a lady approached me and she sent me her gut test, like gut microbiome test. And she told me, Listen, I've been on anxiolytics for the last nine months. And for 12 months, I've gained I think she said 15 kilos. And I've been feeling extremely bad. And when I looked into my gut microbiome, there are some key microbes missing, she had literally had bifido bacterium not detected. Like E Hallii also not to detected. So there are at least five microbes that weren't detected, and just to be cautious. They weren't detected also in two different tests. So two different companies, they show the same more or less results. So in this case, when you have somebody missing a key microbe like Bifidobacterium, you can tell them to take fermented food, which will repopulate. But it will be also, let's say, helpful to have supplementation with probiotics, diverse one, not just one could be a mixture of Bifidobacterium, lactobacillus, or at least the one that available today, to kind of let it help getting that back to the level. And not all of it will colonise. But at least some of it will might stick there and might improve. And there are some studies actually today that showed for instance, that one single bacterium could improve weight loss. We're talking here about a clemencia ministry that there is a company here in in Belgium actually commercialising that, and it showed clinical studies that taking this microbe, which actually was even dead, not even alive, and improved weight loss, there are other companies actually doing some similar studies that showed some key microbes, if their, their mechanism of action is well identified. They could improve mental health, they could improve weight loss, and other disorders, for instance. So it's not a clear cut, as you said, it is also strain dependent. So that's some strains, they would work some others wouldn't. It is also human or patient dependent. So if a patient actually lacks that microbe, it will work on them. But let's say if you already have tonnes of Bifidobacterium, taking probiotics of busy bacterium will do nothing. Yeah.

Peter Williams: 43:45

And I think this is the this is the exciting thing about more precision medicine, because, you know, I can think about the type two diabetics. Where, and even the obese patients where, you know, some strain, some strain specific bacteria may be associated with, Akkermansia, being one of them. And there's definitely a couple of companies in the US that I know now are almost producing the strain specific bacteria that act like a GLP-1 inhibitor, like semaglutide? It's super expensive. I mean, you know, they're really expensive to buy. True. But, you know, I think about that, and you think about, well, is this is this appropriate for this patient? But if you've done the stool tests, and that stool test shows you, yes, these are missing, then thats really becoming super precise medicine that you can look back and say, Yeah, listen, it's going to cost you 200 quid a month. But, you know, we've got as good a chance as we're ever going to get based on the data that we've got. And I think that's a super exciting thing about this. I think it's a super exciting thing about utilising strain specifics. And, you know, you go back to some of the guys that you mentioned, like, you know, John Cryan, at the Cork Institute the microbiome Institute there, I mean, they've done some amazing stuff on, on mood regulating bacteria. They wrote the book didn't they, The Psychobiotic Revolution, which I still think is an incredible, I think everyone should get that one. So talking about that, because, you know, one of the key things for me with regards to health in general is the underlying concept of bacterial translocation, you know, bacteria being able to, you know, move from locations, but also to be able to move the specific metabolites along crazy pathways like the gut skin axis, you know, first of all one, which I mean, I'm sure you're probably certainly one of the experts on, I mean, how the hell does that work? So maybe, because we want to give, you know, because a lot of this feels so sort of sci fi, when you're talking to patients, it's, it's so, you know I think Jesus, are they going to think I'm nuts, because some of this feels like almost like, this can't be real. But it is, you know, I mean, again, if you take something, I mean, you talked about the short chain fatty acid butyrate not only does it have a localised effect on helping the microbiome, it moves off and really helps the blood brain barrier, but helps their brain as well. So can you talk about some of those concepts?

Dr Amine Zorgani: 46:18

It is, it is totally not sci fi. Yeah, it happens. And it is definitely happening. Simple example, as you've said, John Kryon, I think it was one of the earliest also did with, I think, from a Japanese university, where they basically took mice and they cut the vagus nerve of mice and they saw that the communication actually stopped between the gut and the brain and the mice became, you know, kind of crazy simply because there was no more of, you know, kind of molecules feeding the brain, which are mood regulating. And there are so so the, the molecules that produce in the gut, obviously, they communicate in a variety of ways, short chain fatty acids, they are small molecules, they can travel through your body through the gut lining, and they get to wherever they need to be, they can even be detected on skin as well. So butyrate, it is detected on skin in reasonable quantities that are not much butyrate producers on the skin, so it is coming from somewhere else and somewhere else is the gut. So how it gets there. But let me give you a very practical example. So, it is believed that milk from breast when women are breastfeeding, a lot of people believe that breast milk is microbe free, so it doesn't contain microbes. Yeah, but it's not right. So babies get one of babies when they're born, they born more or less sterile. They get first colonisation if they're born with natural birth from the vaginal microbiome. If they're born with a C section, it is different thing. But studies showed that babies that are born by C section, or born by natural birth after a few months, so in the beginning, they have the gut microbiome quite different. So the babies with the vaginal microbiome or the natural birth, they get very nice colonisation, and they have some bacteria already in the gut, which are mostly from the vaginal microbiome. But the babies with the C section, they get very little gut microbes. But studies showed that these babies with a poor microbiome, the C section babies, they get to almost the same level as the babies who are born naturally. The question is why? Where did these microbes from the C section babies who missed kind of seeing these microbes in the beginning they came from. They came from the breast milk. So basically, when the women start breastfeeding, the baby start getting some of the key microbes and they start colonising their guts. The question is now, where did this microbes that in the milk came from? Because the milk I mean the the gland is not producing bacteria with the milk they just produce milk. There are different theories, there are theories that shows that some oral bacteria can also travel and they colonise as well or they get with with the breast milk, but one of the most promising theories is that there are some dendritic cells in the gut, they selectively select some key microbes, they know them for some reason, and they translocate them through our you know, system to the breast where these microbes get transferred afterwards to the baby, as well as through the suction of the mammals. And this proves to you that microbes can actually translocate from the guts with means like dendritic cells, dendritic cells is like you know like sponge. They capture pollution from the skin But they can also capture microbes from the gods, and they translocate them to up there. How they do that it is today not known, like no one knows how this big these dendritic cells, how do they select this bacteria or that bacteria? How do they actually get them from the gut, to the skin to the mammal glands to the baby to the baby, obviously, they get released there. We don't know that. But we know for a fact that dendritic cells can select microbes from the gut, and translocate them. And this is just one example to name a few. And obviously, there is always a connection between the gut and the skin through a variety of ways one of them dendritic cells, as I mentioned.

Peter Williams: 50:39

So when we're talking again, it's really interesting what you said about C section babies, of course, they don't get the best start in life, which is why a couple of you know, you tend to see more of the atopic to sort of skin disorders from that side. Are there any bacteria that strain specifics that you would look to treat skin disorders like psoriasis, or eczema where, the literature looks pretty good. And you know, is that through a probiotic? So it goes into the gut? Or would it be better delivered in some kind of products straight onto the skin?

Dr Amine Zorgani: 51:15

Topically you mean? Yeah, so. So in the case of the skin microbiome, it is much easier, I think, to moderate and much easier as well to use probiotics simply as I said, because you apply it straight on the face or straight on the skin, whatever the condition is. And we are there is a wealth of data showing that there is a clear correlation between the reduction of some key microbes in the case of psoriasis, atopic dermatitis and so on. So, if you identify with these key microbes that have been reduced, you could just repopulate the skin naturally using probiotics or target approach, and here you would use probiotics that that you isolate from healthy volunteers as I said, and then you would apply them in formulations or cosmetic formulations to treat to date there are none on the market. There are none of probiotics that can target skin disorders. Although that I think there is at least two or three, phase two clinical trials using live bacteria, for treatment of skin disorders. And but there are I think, healthy ways of doing this is you know, probably pick your, your, your shampoo, pick your, you know, your your, your makeup or whatever you wearing. Try to as well be exposed as much as possible to nature to you know, be in the forest and so on. Maybe you get some microbes there that will enable you but more importantly speak with your doctor that will enable you to kind of pick the right treatment. But unfortunately today there are none, which I know of their therapeutic however there are cosmetic, let's say probiotics that can treat some skin disorders, some skin sensitivity will have some itching or some redness of the skin. And we also have been in the in the space we've have this acne treatment which because of the cosmetic regulations, you cannot call it as a drug. It is a cosmetic ingredient. Okay.

Peter Williams: 53:25

Interesting on that side, mate, listen, I think we could we could go on for hours and just on this I would love to have you as the the resident expert that we can come back to because there's so much that we haven't covered that I would like to cover so we've done a little bit on the skin which I think is amazing what you guys are doing with that company as well. Highly interested since I'm a man in his early 50s getting a bit wrinkly now and would still like don't look like Yeah. You know, it makes makes you look a bit better on the on the podcast. Yeah. If if what would what would be your sort of, I mean, you are as you say, an expert in this field? What would be your top three or top five simple things that you know people who have no real medical background, you know, just trying to get healthy what what would you say would be the most important things to do to just help your overall microbiome and we're talking everything you know, all surfaces here not just skin, not just GI what would be your, your sort of top tips.

Dr Amine Zorgani: 54:41

Number one, educate yourself. So this means that don't get the information from anywhere or everywhere. Right so a lot of people I see them all go into Tik Tok and that is this hashtag I've read this morning was like from insane gut health. Got 4.5 billion hashtags, on tick tock. So there is a lot of hype about gut health, which is amazing, so many people are being conscious about it. But my tip number one, educate yourself on the microbiome or where you get information from, because the minute you identify a source, it could be anybody that are influencing into the field or scientist, or some people like yourself, you know, really active on the space, and so on. Try to educate yourself about the microbiome. And it's important for your overall health and it can be, as you said, everything like to the basics, removing your shoes, outside your your place, or your home, could help you to be healthier, why you're running outside every day or working. And when you go to the public bathrooms, and so on, you bring those pathogens with you on your the bottom of your shoes, removing your shoes outside, can prevent having pathogens inside, and having passengers transmitted to you or to your toddlers and so on. So that's education. Number two, habits, habits, habits, so everything that is you do without thinking it is a habit. So identify some key habits that will enable you to stay healthy, or to keep your gut healthy. If you go for grocery shopping, maybe try to go to the market to the farmers market where you can get like fruits and vegetables that are fresh, and you know, they seem the sun and so on. If you feel that you actually are a little bit obsessed about eating, you know, nasty stuff, sugars, and so on. Maybe don't put them into your site, just remove them away, or hide them or maybe dump them if you could, just that you get the habit of actually educating your body. So educating your brain is understanding about the microbiome, educating your body of resisting the temptation of eating processed food a lot. I mean, not telling you to not to go to this, you know, not to name the companies wherever to get processed food from outside, you could maybe get one, once a week, you know, weekend maybe you could have a night out and have, you know, these cheesy burgers and whatever. But don't make it a habit to do that every day. Don't make it a habit to drink Coke every day. Because it just a lot of processed food, you throw it in the inside, make it a habit, maybe to diversify your food, make it a habit to eat some nuts, make it a habit to I don't know, one and the other things from habit perspective, which people actually do miss a lot. I know people, they never change their toothbrush. Right? Oral Health, the oral microbiome is known to drastically influence the gut microbiome, which also influenced your brain function. And having a toothbrush, which is let's say, dirty, or I mean, there is biofilm in it and so on, won't help you changing your toothbrush, you could put this, you know, as an arm into your phone, changed my toothbrush every two months, I would just in two months change it afterwards, and so on. So this is just from a habits perspective. And number three, which is people tend to look at as most difficult one which is actually isn't a difficult thing, exercise. Because the more you exercise, ideally, outdoors, when I'm not telling you to run a marathon, I'm just telling you go out for half an hour at least or 30 minutes, which is the same a day walk with your dog or with your baby or the with your wife or with yourself as well. Exercise. Exercise is not just physical exercise, there is also mental exercise. We also know that meditation, for instance, has very positive effects. I mean, there are studies that published recently in nature as well showing that Buddhists they have a different and a diverse gut microbiome. Not sure who influenced what but at least that you know that meditation can actually improve. So there is body exercise and mental exercise. And I think these three tips I would say, educate your brain, educate your body, and keep some habits.

Peter Williams: 59:15

I think that's a brilliant place to stop. But certainly, I'd probably say part one of many parts, I think on that side. Amine, thanks so much mate, that was that was amazing. And sort of I was pumped all the way through there. So I just think there's so many questions that we can bring you back on so many areas that you're going to be in that we can if you're okay with that we bring you back on, Yeah, mate. Just just learn a little bit more about all of this. It was a great pleasure. Thanks so much.

Dr Amine Zorgani: 59:52

Thank you. Thanks. Good