Episode 031 - Dr Petra Louis

The following is a conversation with Dr Petra Louis, Senior Research Fellow at the Rowett Institute for Nutrition and Health at the University of Aberdeen.

We entertained various subjects in a fun, but also quite serious manner. We got into some nitty gritty fun topics with regards to diets, supplements, fibre, and all the things that we've talked about before in the podcast, but going into quite some significant detail. For those of you who are taking supplements and interested in longevity and healthspan, this would be a good episode for you.

I wanted to take this opportunity to thank all of the listeners and supporters of the podcast for everything you've done to help us build the name, and the brand, and to get the message out there around microbiome being critically important and gut health being really important for wider body health.

Timestamps:

00:00:00 Introduction

00:02:06 Interest in the microbiome

00:05:23 Research into E-Coli

00:13:29 Dark matter in microbes?

00:16:12 Is Oxygen toxic for organisms?

00:23:57 Polyphenols

00:26:19 Role of supplements

00:30:27 Preventative power of supplements?

00:35:31 Pushing lifespan beyond what’s normal

00:39:02 Health span vs lifespan

00:43:37 Life as a CEO

00:46:42 Fibre and butyrates

00:51:42 Resistant starch

00:55:02 Soluble and insoluble fibre

01:00:02 Eating whole foods vs processed

01:06:06 Pro and prebiotics

01:10:07 Creating short-chain fatty acids

01:11:36 Are all fibres prebiotic?

01:15:20 Cooking vs raw food

01:18:13 Future understanding of nutrition and the microbiome

01:21:36 New dietary recommendation in the future

01:23:39 Keeping up with scientific papers

01:26:09 Will disease be cured in the microbiome?

01:31:06 Just keep on top of your diet

Full Transcript:

[00:00:00] JAMES: The following is a conversation with Dr. Petra Louis, Senior Research Fellow at the Rowett Institute for Nutrition and Health at the University of Aberdeen. I was really excited to have Petra on this podcast. She was actually the first academic working in the field of microbiome science that I spoke to about antibiotics.

[00:00:17] JAMES: And I'll never forget that meeting that I had with her, where I shared my vision for transforming the microbiome through full spectrum therapeutics in what was then the old Rowat Institute near the airport in Aberdeen. Because I've known Petra for so long, this was a really engaging conversation that I think you'd expect friends to have actually.

[00:00:37] JAMES: And we entertained various different subjects in a fun, but also quite serious manner. And we got into some nitty gritty fun topics with regards to diets, supplements, fiber, all the things that we've talked about before in the Therabotics, but going into quite some significant detail. Since the conversation, I've actually rethought how I manage my supplement stack.

[00:00:59] JAMES: [00:01:00] So for those of you that are taking supplements and interested in longevity and healthspan, this would be a good episode for you. For those that are supporting the podcast, I just wanted to shout out and say thank you very much. I've recently reviewed my metrics and was really pleasantly surprised actually to see how many people were listening to each episode and also how far and wide my listener base was from around the world.

[00:01:22] JAMES: Quite stunned actually to have listeners as far away as Singapore and other parts of Asia. So just wanted to take this opportunity to say thank you to you all for supporting the vision and the mission. I really appreciate it. The best way. To support the podcast is to listen, but also to share with your friends, to like and subscribe, and to give a five star review if you haven't already on your favorite podcast app.

[00:01:43] JAMES: I'm open to suggestions for how to make things better looking forwards into the future, so please reach out to me on socials or directly through the email address james at insidematters. health. This is Inside Matters, my name is Dr James McElroy, I hope you enjoy it.[00:02:00] 

[00:02:06] JAMES: How did you get interested in the field of the microbiome? 

[00:02:09] PETRA: So When I started my research career in Germany, uh, where I did a diploma degree in biology, I ended up in a, in a lab that was working more on microbial biotechnology and specifically on compounds that are made by microbes that live in high salt environments, so salt lakes such as the Dead Sea, let's say.

[00:02:30] PETRA: So these environments are essentially very, very dry environments because of the high salt concentration, the cells basically dry out. So very few organisms can actually live in these extremely high salt um, conditions, and we're talking much higher than seawater, so maybe ten times more salt. in a lake like the Dead Seas.

[00:02:51] PETRA: I think it will be more than 10 times. But anyway, it's much, much saltier than seawater. So the, the organisms that [00:03:00] can actually survive and even grow and multiply in these conditions, they need to have mechanisms that they can actually survive there. And one way of doing this is by accumulating in very high concentrations molecules inside so that there's osmotic balance across the membrane.

[00:03:19] PETRA: And one strategy is to use these organic molecules and they're called compatible solutes because they are, despite the fact that they're present in very high concentrations inside the cell, they're still compatible with the cell being still able to do its cellular functions. So they're not really messing with the biochemistry that happens inside cells to let them grow and divide and all this.

[00:03:43] PETRA: Why 

[00:03:43] JAMES: is that? Have they got like special compartments within? Their membrane to sort of keep them separate or is it just they're at such low concentrations they don't interfere with the the normal physiology? 

[00:03:52] PETRA: No, the concentration is extremely high. It's really more that they seem to not interfere with enzyme function, for [00:04:00] example.

[00:04:00] PETRA: So there are actually some bacteria, there are some microbes, not bacteria, archaea, that actually let salt in. May not be exactly the same salts that are outside, but you know, they may have a lot of potassium inside and chloride. But they had to really adapt their protein machinery completely. So you can see that actually the protein.

[00:04:17] PETRA: composition is different. They have many more charged amino acids to sort of neutralize these salts that are inside. But they're kind of obligate extremophiles, extremophiles are organisms that can live in extreme conditions. Whereas a lot of the bacteria use these organic compatible solutes and they're just, they're just less inhibitory to enzymes.

[00:04:40] PETRA: They work better with our normal enzyme apparatus and our general, our organic molecules that make up our cells. And I'm saying our, I mean, obviously bacteria here. Um, so that's just a different way of dealing with it. And these, these all sorts of organic molecules. One, for example, is glycine betaine. [00:05:00] And that's also a molecule that I think we have in our metabolism somewhere.

[00:05:05] PETRA: So they sort of adopted different molecules. Other ones use also glutamate. which is an amino acid. And then in my group specifically, we worked on a specific group of compounds where the compounds had been found. But in those days, we didn't really know the genetics. We didn't, we knew the bacteria who made it.

[00:05:23] PETRA: So in my PhD, I looked at the molecular biology of finding these genes that make these compounds. But before into my diploma, I actually worked on a much more biotechnology, applied project where I was looking at can these solutes be used, applied, um, to preserve organic molecules or organisms. So somebody else was looking at can they preserve enzymes, you know, for biotech companies, and I was looking at can they preserve organisms, and you know what the organism was?

[00:05:54] JAMES: I'm going to hedge a guess. E. coli. Yes, it's E. coli. [00:06:00] E. coli, Nissa, 

[00:06:00] PETRA: 1917. Oh wow, no way! 

[00:06:04] JAMES: Only proper microbiome enthusiasts will understand the significance of what you're talking about. I know! I'm glad I got it right. I was thinking E. coli because it's like the workhorse of, you know, biotechnology and Nissa.

[00:06:19] JAMES: Good thought. Which kind of makes sense because Well, it's in Germany, and they love E. coli in Germany, so for the listener, sort of try and contextualize all of that. 

[00:06:29] PETRA: So a previous PhD student in the group had gone on to that company that manufactures E. coli in 1917, and this is 1917, and so this is a strain of E.

[00:06:40] PETRA: coli, which is sort It's used as a so called probiotic. It's a live bacterium that people can, um, consume to keep their guts healthy. And particularly it's often used for traveling. So if, or also diarrhea. So I have had another of my mates from Germany who later on worked in the company and he always had some in the fridge at home for his [00:07:00] kids.

[00:07:00] PETRA: So if the kids were getting an upset stomach, he would have it right ready there. And you know the story where it comes from. No, it was isolated from a soldier in 1917 who went to, I can't remember exactly where he went, but actually as part of the war. Um, so I, I never read the summer, but that's the story I still remember from the soldier selected because he never got a next 

[00:07:33] JAMES: gen probiotic They were on it back in 1917 because one of the critiques is Well, Lactobacillus, Bifido, well, the reason that they're in quote unquote probiotics is because they're stable in yogurt and cheese and milk.

[00:07:46] JAMES: But this sounds a bit more sophisticated. Somebody at some point was like, that soldier, 

[00:07:51] PETRA: he's so healthy. I know. And 

[00:07:53] JAMES: they took a stool sample and they isolated it and that was then what has become. Quite a popular probiotic. [00:08:00] Yeah. Now one question, do you take 1970? 

[00:08:03] PETRA: I don't really know. You don't take any probiotics or?

[00:08:07] PETRA: No, I don't need sort of probiotics that are marketed as, you know, I don't go to the pharmacy and buy probiotics. Um, yeah. It's very difficult to get non probiotic yogurts these days, so I do quite like a yogurt once in a while and if it's probiotics and that's, that's fine with me. It doesn't bother me, but I'm not buying it for the probiotics.

[00:08:28] PETRA: I'm looking more for, you know, I want sort of natural yogurt. I don't want the zero fat and the zero sugar because it has some other stuff in it that I don't want. So I don't mind the probiotics, but I don't take them because I think as a healthy person with a healthy diet. I don't need a probiotic, but obviously for certain indications, for certain problems that people have, I think probiotics will be one avenue to take that will help some people.

[00:08:55] PETRA: Absolutely. 

[00:08:56] JAMES: Now, back to E. coli 1917 and [00:09:00] your journey into the microbiome. So what happened 

[00:09:02] PETRA: next? So after this whole, the years in the extremophile field, I wanted to move on to another lab and I wanted to work on something related but not quite the same. So I actually ended up in the end, after looking at options in Aberdeen, in a lab that was working on E.

[00:09:21] PETRA: coli, NISL 1917, just E. coli generally, um, and stress, stress regulation. So you know, I moved away from that extreme, extremophile, which was fun to work with, but we had nothing. And also in those days, we didn't tend to have genome sequences, but, and all this. So we had much less information about the organisms then, we're talking sort of.

[00:09:44] PETRA: late 90s here. Um, but for E. coli, there was already much more, there were more tools and all this. So, you know, with my organism, I, I tried for the first two years of my PhD to get genetic transfer methods, which you need if you want to [00:10:00] really look into the detail of gene regulation, molecular biology, and I didn't succeed.

[00:10:05] PETRA: So I, you know, I had PhD went okay, but that thing. didn't work out. So I was quite keen on going into a lab where I can really get more into the nitty gritty on a sort of model organism, but it wasn't extremophile in that sense. So I did a postdoc there, moved then on briefly to another postdoc. Why 

[00:10:23] JAMES: is E.

[00:10:24] JAMES: coli such an interesting organism? 

[00:10:27] PETRA: That's a good question. I think it's part of it is probably serendipity. I don't know. I've never really looked into the details, but it's quite easy to grow. It is a gut bacterium, but it also grows very happily outside. It can grow in the presence of oxygen, in the absence of oxygen.

[00:10:44] PETRA: It doesn't have too many needs. It grows very fast, although obviously different strains will be different, they're not all the same. And they can be vastly 

[00:10:53] JAMES: different, right? Yeah, absolutely. You can have the 1970s until 1917 and then you have [00:11:00] 0157 which can give you really advanced kidney disease and maybe kill you.

[00:11:04] JAMES: Yeah. Absolutely. Absolutely. Absolutely. Absolutely. So is it, is it kind of unique in that regard with so much variation across the strains or is it just we've studied it lots and? 

[00:11:13] PETRA: It's a good question. Again, I haven't really looked into this in detail. I think there's some species where probably most of the strains are.

[00:11:22] PETRA: pathogenic as in disease causing or not. I'm not aware, for example, of any bifidobacterium that has caused disease. I don't think so. And I'm now, for example, looking at listeria as another sort of food borne pathogen. I'm not aware of of non pathogenic listeria. But now that I'm saying this, I'm not too sure.

[00:11:47] PETRA: Microbiology is very complex. So, um, it's probably partially also because it has been studied so extensively, but also business lifestyle being very versatile. It will have had evolutionary, a lot of [00:12:00] opportunities to adapt to different niches because it can just end up in a different environment. And it's already so versatile that it will not immediately be killed.

[00:12:10] PETRA: And then it maybe has time to adapt to these different 

[00:12:12] JAMES: environments. Yeah, that makes sense. So, sorry, back to your work. Yes. I'm sure we'll talk a lot about E. coli and why it's important. I guess, just one more point. Is there still a lot we don't know about E. coli? Is there still a lot we don't know about microorganisms?

[00:12:30] PETRA: I think so. So I, I left that I had another brief postdoc, but then I moved on to the gut field in 2002, I think. So it's a long time ago for me to have looked at E. coli in detail. I can't really tell you, you know, I never looked nowadays at the databases in E. coli, but in, in principle, I think even for, bacteria like E.

[00:12:49] PETRA: coli, we still don't know if you look at the genome, for example, we still don't know what all the genes do. And some bacteria will be more understood than others. And I'm sure in a model [00:13:00] organism like E. coli, there are groups who either have or are in the process of knocking out, so basically destroying individual genes.

[00:13:08] PETRA: to see what does this gene do, but I assume that still in E. coli, there will be a lot of genes we can see from the sequence in a genome where a gene should be by looking at, basic characteristics of the DNA sequence, basically. But then we know, oh, this should be a gene, but we may not know what it does.

[00:13:28] PETRA: And, you know, some bacteria like E. coli also, maybe some yeast like Saccharomyces cerevisiae, a lot of this very fundamental work is done. But I think there's still, um, for example, genes out there that we don't know what they're doing. So there's still some dark 

[00:13:43] JAMES: matter in the genome of microbes. I think so.

[00:13:46] JAMES: Just like there is in our own genome. Right. There's lots we don't understand in terms of how does it work and, you know, we're like 98 percent genetically similar to a banana, but we're very different to a banana, right? So there's a lot that we don't understand. I think maybe we should touch on the [00:14:00] genetic diversity element just a little bit because I mean, my understanding is that there's vastly more genetic diversity.

[00:14:07] JAMES: in the gut microbiome than there is in the human genome, like one or two orders of magnitude. Um, and when you got started in the field, what, where were kind of, where were we, if you like, in 2002, I think, 

[00:14:21] PETRA: as you said. Yeah. 

[00:14:22] JAMES: Yeah. And if you can also contextualize it and what we were talking about before we started around the hype.

[00:14:29] JAMES: Where were we on the hype cycle at that time, 

[00:14:31] PETRA: you know? Yeah. So when I moved on, that position at the Raoult Institute became available and I was very intrigued by it. Um, so I applied for it and for me it was really quite a big change because up to then I had always worked on like one organism. Yeah.

[00:14:46] PETRA: That was my pet and I was trying to work out something about how it functions, what it does. Right. And this obviously was a huge step change. And also I'd never worked with anaerobes before. So I went from working with aerobic organisms, which are organisms that [00:15:00] live in the presence of oxygen. to strict anaerobes, which is technically quite a big change.

[00:15:05] PETRA: So strict anaerobes are those most of the bacteria in the gut are strict and in the lower intestine at least are strict anaerobes, which means they are killed by oxygen. So they would not survive. On this desk. For how long? Um, it, it's different. So I think my colleague Sylvia Duncan has done some studies.

[00:15:24] PETRA: So she plated all different bacteria in an anaerobic cabinet, which is basically a box where you can control the gases that are inside. And you stick your hands in through, through gloves to manipulate them. And, uh, she literally plated them out, took them out, put them back in, and I think the quickest she could do this was a minute, I think.

[00:15:45] PETRA: And some of them were literally, had already gone down by logs. Yes. And others, you can see that the sort of death curve over time, you know, is, is a bit less dramatic. So it really [00:16:00] depends on the bacterium you're looking at. So it really depends. In, as a general rule, the Firmicutes, the gram positive bacteria, tend to be more oxygen sensitive.

[00:16:08] PETRA: But within those, you find differences, and the bacteroides may be a bit better. Do 

[00:16:12] JAMES: we know how they die? Like, what happens? Do they, like, 

[00:16:15] PETRA: explode? Yeah, basically, oxygen is toxic for organisms. It's toxic for us, too. I know that. I better stop doing my Wim Hof hyperventilation every morning. Oh yeah, I'm not sure 

[00:16:28] JAMES: that's good.

[00:16:28] JAMES: I do it every morning. I'm not joking. Yeah, I heard it's good. Every morning, I'm not joking. It reminds 

[00:16:33] PETRA: me of Howard and 

[00:16:34] JAMES: Maud. Even in weird places and people look at me and they go, what is that man doing? Is he having some sort of anxiety? Yeah, I think it's called Tibetan fire breathing. Okay. So you sort of, so you hyperventilate for like 30 or 40 breaths.

[00:16:51] JAMES: Then you, like, uh, squeeze, it's like a Valsalva maneuver. And then you hold your breath for as long as possible. And then you repeat. [00:17:00] Now, what are the benefits? Well, you're hyper oxygenating your blood, you're maybe changing the acidity alkalinity, then you're holding your breath and it's probably becoming more acidic.

[00:17:11] JAMES: There's some element of deep relaxation that comes with this, probably to do with the vagus nerve, I think. And Wim Hof, who's a sort of Western modern day superhuman, do you know who I'm talking about? The 

[00:17:27] PETRA: Iceman. Oh yeah, yeah, yeah. I do know. Iceman, yeah. He is 

[00:17:32] JAMES: a medical and scientific marvel. So he, he, you'll, you'll enjoy this one I think because you're a microbiologist.

[00:17:39] JAMES: So, so when he started coming out and doing his things, people thought, oh, it's, this is just Wim Hof. You know, he's able to. be in an ice bath for like an hour. It should be impossible. He's ran marathons with no like additional water. He, um, climbs mountains with just shorts on. [00:18:00] He's also able to somehow train his immune system through this breathing in the cold.

[00:18:05] JAMES: So, so he, he's been injected with endotoxin and there's been no physiological response, just super high antibody titers. And then, then they said, Oh, it's just you. You're special. He said, no, I'm not. I can teach other people. So, so there is an experiment which I can send you. I think it was published in nature where they split the groups and one had the Wim Hof training.

[00:18:25] JAMES: The other didn't have the Wim Hof training. They were given endotoxin and Wim's group who'd have his training that didn't have a systemic inflammatory response syndrome. Wow. Which seems impossible. Yeah. 

[00:18:35] PETRA: But anyways. So is this controlled through the mind? Must be. So, 

[00:18:41] JAMES: so, so breathing is both autonomic and conscious.

[00:18:46] JAMES: And I think the deep breathing and control over your breath allows you to start to tap into your autonomic nervous system. It has some impact on vagus tone and vagus control. What it does to the immune system, I don't think we know, but I think it does good stuff. [00:19:00] Anecdotally, it gets sick much less often.

[00:19:03] JAMES: Anecdotally improves resting heart rate. I think it's quite good for anxiety and things like that, whether it's the cold or the breathing, I don't actually know. I really recommend it. But you just told me oxygen is toxic. So 

[00:19:16] PETRA: first thing you tell me, how long do you do that for? Right. Uh, 

[00:19:20] JAMES: so probably for 15 minutes every day.

[00:19:23] JAMES: So you go through cycles. You go through cycles. So it's like two minutes and then hold your breath for two minutes, two minutes, hold your breath for two minutes, sometimes three minutes, sometimes three minutes. And this is a big movement that this, now I do know that the actual oxygen content of the air is not as high as some people think.

[00:19:38] JAMES: I don't know what the exact figure is. I think it's more like. It's 10 percent or something like that. And then the rest of it's, you know, other inert gases. 

[00:19:46] PETRA: It's about 18 I think. Nitrogen mostly and a bit of CO2. Yeah. 

[00:19:52] JAMES: And there's a tiny bit of things like helium. I think tiny, tiny elements like that. Yeah.

[00:19:59] JAMES: So 

[00:19:59] PETRA: why is it [00:20:00] toxic? So it's intrinsically toxic because during the metabolism, it, there's radicals are formed. You heard of radicals before. So they are basically molecules are broken. And, uh, bonds in chemistry always want to be in pairs. I'm not a chemist. I'm not explaining this badly. So basically the, the, the molecules are broken apart in a way that a single electron is sitting there and one's desperately find another electron to make a pair again.

[00:20:28] PETRA: And, uh, during the whole, metabolism, these molecules are formed and then they're attacking DNA proteins and doing damage. So it's a complex one because we obviously need oxygen. So we need oxygen to survive, but in principle, yes, without oxygen, we couldn't, we couldn't get energy. Yeah. We would die very quickly.

[00:20:50] PETRA: Obviously. Electron transport is all part of the same ultimately. Yeah. So it's the final. the final acceptor of [00:21:00] the electrons that are flowing through. When we're breaking down our food and doing all the oxidation reduction reactions, then oxygen is the final one and it turns into water, right? But inherently it is toxic.

[00:21:12] PETRA: Yes. So during that process, there are radicals formed. So, um, I mean, I think it's really the whole toxicity thing is a fascinating topic in its own right. So we do need oxygen. We have obviously evolved, to cope with the oxygen. Maybe if you're going right back to the start and think of the salt loving bacteria, you know, they obviously have coped also with something and it's no bother for them anymore.

[00:21:36] PETRA: I don't know. Do they need the salt? They don't really need the salt. So I was just thinking, it's probably not, not really a good analogy actually. Um, but the archaea that I depend on the salt, they basically need it now. They couldn't do without it anymore. The archaea, very interesting. The archaea that actually accumulate.

[00:21:54] PETRA: accumulate salt inside. They had to change the whole, um, by chemistry to do that. [00:22:00] So they adapted to that environment the same way as we evolutionary have adapted to, Oh, there's suddenly loads of oxygen. I don't know how many million or billion years ago. Plants made all the oxygen, the organisms adapted to the oxygen, right?

[00:22:13] PETRA: So, They made use of it, but at the same time, the biochemistry intrinsically is quite damaging. So they had to do something to counteract it. So our body is full of, um, stress response mechanisms. So we have these antioxidants in us, um, vitamin C, for example, and they are there to mop up these. radicals all the time.

[00:22:33] PETRA: We also have enzymes and these anaerobic bacteria in the gut don't have them. And also oxygen tolerating bacteria have these enzymes that neutralize these radicals. Yeah. So there are enzymes that, that take away the radicals so that action doesn't happen anymore. cell constituents or molecules are damaged in the first place, but any damage that has been done, there will also be other systems cranked up that can repair [00:23:00] the damage.

[00:23:00] PETRA: So as long as you don't overdo it, and I'm not an expert on your breathing, so I don't know if it makes you feel good. It makes you feel good. That's fine. 

[00:23:09] JAMES: It should be fine. Strong when I do it. But there's also some element though of, Low level of cellular stress being a good 

[00:23:17] PETRA: thing. Yes, I was going to.

[00:23:19] PETRA: Because it sort of triggers 

[00:23:20] JAMES: spring cleaning and, you know, clearing out bad cells and repair. Yeah. You know, repair and test, repair and test. So. 

[00:23:29] PETRA: And we are always, So, you know, the, the oxygen is a very simple example, but we're constantly in the environment, potentially exposed to something. So if our stress responses or stress coping mechanisms are sort of already there a little bit induced, you would say, you know, if they're not dormant and the body has to react first, if you are hit by this toxin or this toxic substance, then your body can deal with it more quickly.

[00:23:57] PETRA: And that's actually one theory whole. um, a lot of [00:24:00] plant secondary molecules. These polyphenols work. Yeah. We don't really know how they work and how much is it an antioxidant effect? How much are actually these polyphenols cranking up or, or, uh, stress responses, or it may be something else altogether. So one theory is that basically they're actually slightly toxic for us.

[00:24:20] PETRA: We see these things coming in and saying, 

[00:24:22] JAMES: Oh, really? I like 

[00:24:24] PETRA: this one. I'm not an expert in polyphenols. You need to go to some of my colleagues for that, but that's what I understand from my general reading, that it's one theory and then probably many different mechanisms in how these polyphenols work.

[00:24:39] PETRA: Including 

[00:24:40] JAMES: the microbiome chewing them up? 

[00:24:42] PETRA: Well, so they're, as far as I understand, they're not really a major food microbiome, but the microbiome may have enzymes that convert them. So it's called biotransformation. It's not really, this is a food for me so much. Cause they like the fiber. Yeah, they're like the fiber.[00:25:00] 

[00:25:00] JAMES: We're going to talk about that too.

[00:25:04] PETRA: So yeah, one idea is that maybe it's actually a system, a mechanism to say, yeah, actually this isn't, it's potentially not good for me. The amount of food we're eating is cranking up these stress coping mechanisms, but not really making us ill. So it's a good thing. That's so 

[00:25:23] JAMES: interesting, isn't it? I know it is.

[00:25:24] JAMES: Because some of these, some of the most polyphenol dense foods are stressed plants, like the purple broccoli for example. So they're stressed, we're eating them, it's making us a little bit stressed. In 

[00:25:36] a 

[00:25:36] PETRA: way, yes. In a way? Yes. Nearby chemistry. 

[00:25:38] JAMES: Is there some sort of deeper meaning there? No, I think we're going a bit off piste there on this, uh, on this podcast, but 

[00:25:45] PETRA: no, not at all.

[00:25:46] PETRA: I like to explore that a little bit. But you know, it makes sense, isn't it? Because the plants do it as a coping mechanism to not be eaten by bugs, insects or whatever. Because it's toxic. Yeah. And you know, we also have plants which we can't eat at all because. it's too [00:26:00] toxic for us. So when you then heat it up, you destroy that toxin.

[00:26:03] PETRA: I'm not sure whether they're all polyphenols, but let's just say in general plant secondary compounds, it could be one way. Um, how, and I forget now what all these enzymes in the gut wall are called, but I think some of them are believed to latch onto these enzymes and trigger them to crank up these. So 

[00:26:19] JAMES: does this mean if you eat too many polyphenols and plants, it might be a bad thing for you?

[00:26:26] PETRA: Again, I'm not an expert, but I suspect normally the amounts we eat is fine. Yeah. Yeah. I'm not worried at all in eating. I 

[00:26:34] JAMES: supplement heavily with polyphenols. Oh, 

[00:26:37] PETRA: so what sort of supplements are you 

[00:26:40] JAMES: taking? Fizetin, quercetin, I had resveratrol for a while, but these, these are flavonoids, you know, these are polyphenols.

[00:26:48] JAMES: I mean, quercetin is quite interesting because It's, it has a number of potential medicinal benefits, which I don't require. Like for example, for people with allergies, they anecdotally [00:27:00] have very strong responses. Now, when we first met as a medical student trainee, I would have said, no, if there's not meta analysis, RCT, I'm not interested because I'm training to be a doctor.

[00:27:11] JAMES: But now I've moved on from the practice of medicine, I'm more open minded and I have actually got a view now, which is that I think it's the anecdote. It doesn't match up with the data, and there's a lot of anecdote, then the data's just not there yet. That is a view I've taken, because if you go to these medical conferences, you speak to a doctor, they say, Oh, we have our pyramid of evidence, and at the bottom is anecdote, and at the top is meta analysis.

[00:27:36] JAMES: And we're not really interested in this as an RCT systematic review of meta analysis, but actually, hold on a minute. You know, maybe it's just we've not done the studies yet and that anecdotes real. So I believe people when they say, well, actually my allergies get way better when I take quercetin. I believe that.

[00:27:52] JAMES: And I think there's health benefits with flavonoids. But I'm going to look into this more now to establish if my extremely high dose of flavonoids [00:28:00] are potentially having a damaging effect. 

[00:28:01] PETRA: I can't say for sure it's not going to be good for you or it's even bad for you, but I wouldn't do it. So my philosophy is, I think along the lines with you, that if it says we don't have the evidence, I wouldn't say don't do it if I don't find negative evidence.

[00:28:17] PETRA: But you know, one thing. thought that is triggered by what you was just saying is for a long time, and you still hear this now often in, in the television, in food programs or something is for example, about vitamin supplements, water soluble vitamins. You can't do any harm. Just take them anyway. Your body will just get rid of them.

[00:28:37] PETRA: And I think That's not really, there's too much evidence now to say that's too simple, it's not true. And I think vitamin C is an example, isn't it? Sports people use a lot of it. And I think the problem is they're actually messing with this whole stress system. Yep. Yes, they're completely messing up the regulation, and again, not my expertise, so, you know, this is on very broad terms, [00:29:00] of this whole, uh, stress inducing, inducing the mechanisms that help the body cope with stress is because it's flooded with vitamin C, and there could be different effects of all this.

[00:29:12] PETRA: So I think one of my major, um, microbiology professors in Germany said quite often, if Um, everything is a toxin. It depends on the concentration. Love that. Right? That makes sense. So I would be 

[00:29:25] JAMES: very careful. Some stress is good. Some stress is good. A little bit of stress is almost always good if it's in the right setting, but too much stress, whatever the trigger, is probably not 

[00:29:34] PETRA: a good thing.

[00:29:35] PETRA: It's not just the stress, it's really having too much of one molecule. So I give you another example of vitamin D. So I take very few supplements, but I do take vitamin D because we're living so far north and all this. And then when I started It's a nice sunny day today 

[00:29:48] JAMES: though, hey? It's a nice sunny day 

[00:29:50] PETRA: today.

[00:29:50] PETRA: Yeah, but in the winter we're not getting any, I'm afraid. So you need to wait till April here so to get any benefit from the sun. The sun is here too weak to [00:30:00] make vitamin D through your skin. Yeah. Well, so 

[00:30:02] JAMES: can I just push back a little bit? It is weaker because it's not as high in the sky. The day is also shorter, but you could get your vitamin D if you lay out in your swimwear.

[00:30:12] JAMES: I don't think so. I think you can. I did a bit of work on this. It's just, it's just, it's not, it's not practical because you get too cold. 

[00:30:18] PETRA: Okay. Yeah. I thought the energy level of the sun rays are so weak that it just doesn't trigger that reaction. That's what, what I read. But you 

[00:30:25] JAMES: should take vitamin D. I agree.

[00:30:26] JAMES: Yeah. So, 

[00:30:27] PETRA: so when I started doing this a few years ago, I took it with calcium and magnesium because you know, it's good calcium, magnesium, you need them. So, and then I came across an article that found, um, and I can't remember the details it's years ago, but it was a randomized study, I think. Um, they found that there was, there must have been an epidemiological study because they found people who had taken calcium supplements had a much higher rate of dementia.[00:31:00] 

[00:31:00] PETRA: Oh, gosh. Was it dementia or heart disease? Anyway, it had to do with clogging up the arteries. Both linked. Both linked. So basically, the theory there is if you take your calcium in form of one pill, Then you get such a massive influx of calcium very quickly into your body because that pill is, you know, like dissolving in your system very quickly.

[00:31:26] PETRA: And that whole dose, which is often what, two or three or however many times daily recommended allowance, they're normally over. overconcentrated. I don't understand why, but yeah, exactly. And then, you know, the calcium, that would be a one daily allowance, which you get a little bit with your breakfast and a bit more with your lunch and a bit more with your dinner and a very complex meal where it will slowly trickle into your body.

[00:31:49] PETRA: Suddenly you get maybe two or three days worse in like half an hour. And that people believe, I don't know whether that's ever been proven, but that was the hypothesis behind it, that you get such a spike [00:32:00] of calcium, um, that your arteries are getting clogged up because suddenly it's unphysiological concentrations.

[00:32:06] PETRA: So my philosophy is very much so vitamin D. Yes, I take fish oil because I don't really like fish. And I have sort of starting arthritis issues and pain issues. So I think for me, that's something I need to take because I don't get it from the diet enough because I don't want to force myself to eat oily fish.

[00:32:22] PETRA: Um, and I also take devil's claw. Um, we can go back to that if you want later. I'm very interested in Devil's Claw. So Devil's Claw, I, I started getting these quite painful, horrible, little knobbly, um, knuckles a few years ago, and my mother had that very, very badly. So um, I just went, when I was visiting in Germany, went through the pharmacies and asked few pharmacists, like, what could I do?

[00:32:48] PETRA: You know, because whatever I had found in my reading, I wasn't really getting anywhere else that I could do because I already eat quite a healthy diet, I think. And one of them said, try this and it's devil's claw. And I think there's [00:33:00] quite good scientific evidence that it is anti inflammatory and really Um, counteracts inflammation arthritis, both osteo and rheumatoid arthritis.

[00:33:08] PETRA: And you know what? I started this two years ago or so. You see benefits? It's, yeah, it stopped in its track. Wow. Pain is gone. Amazing. And, you know, it's also gone back a bit, I think. It's not as swollen anymore as it used to be. That's amazing. It seems to go away. It can interfere with your stomach and I'm a bit worried because long term usage could nobody really knows, you know Is it gonna be okay in the studies in the shorter term studies?

[00:33:31] PETRA: Everything seems fine. But currently my benefit is so much That's 

[00:33:34] JAMES: incredible that what is it? I mean, it's It's, it's some sort 

[00:33:38] PETRA: of plant compound or something? It's a complete plant, it's a plant. It's the complete plant extract. Wow. And again, there's one ingredient you talked about. Corset? No, what's in turmeric?

[00:33:50] PETRA: Curcumin? Curcumin, yeah. So, you know, that's another one. So, that would be the turmeric equivalent. So, I take turmeric in my food. But I don't take curcumin because I [00:34:00] believe after that calcium story and hearing about the vitamins and thinking we shouldn't just think bang it in, it's good for you. I mean, that's kind of unnatural.

[00:34:08] PETRA: And I always think, but what's what's physiologically normal for us? Yeah, I'm 

[00:34:13] JAMES: going to show you after this recording my supplement pill box and you're going to laugh a lot. It's full morning, lunch and evening. And actually. Honestly, the way you've just talked to me about all of that has made me deeply reconsider my strategies.

[00:34:30] JAMES: I'm being 100 percent serious. I mean, really, really, really serious about that. I'm going to really think about my strategy because it just makes so much sense to me now that you've said it like that, that if you dump a whole load of a micronutrient into your body, you are going to achieve a concentration way higher than you would ever be able to achieve otherwise.

[00:34:51] JAMES: Now, the flip side is, One of the benefits of supplements is you're able to do that. So vitamin D, for example, the EPA, DHA in your fish oil, [00:35:00] you know, and the flavonoids, it's really hard to get high concentration of specific flavonoids. So there's, there's a double edged sword to all the supplementation, which is yes, you can achieve supra physiological quote unquote through your diet.

[00:35:13] JAMES: through supplementation. Yeah. But the flip is, as you've said, maybe it has an 

[00:35:17] PETRA: unintended consequence. Do you want that? Do you want more than would be normal for you? If you think back how many hundreds of thousands of years, how people lived, nobody would have been exposed to this. And, you know, Yeah, I don't know.

[00:35:31] PETRA: Do you try to push your life span beyond what's normal? I just want to stay healthy. You know, I want to be as healthy as I can, and I'm worried about the potential consequences of overdosing something because my body is not really evolutionary. I don't think my body was ever expecting to be bombarded with stuff.

[00:35:50] PETRA: And also, you know, think about it in these studies where they're looking at resveratrol, for example, and then say you need to drink whatever, a hundred bottles of wine to get the dose, you need to see the effects. [00:36:00] Well, you know, do you want to achieve that? Because it's not just going to be that one molecule.

[00:36:04] PETRA: That's also why I take turmeric over curcumin. because the turmeric. Oh, you're 

[00:36:09] JAMES: going to say that's why I drink a hundred bottles of wine a week. I 

[00:36:12] PETRA: wish my stomach wouldn't let me do that. I was going to 

[00:36:16] JAMES: say, very good stuff if you're drinking that much. Yeah. 

[00:36:18] PETRA: But you know, is it then still meaningful for keeping us healthy?

[00:36:23] PETRA: If you need a dose that is a thousand fold over what you could ever eat. And if you think for somebody like you, you must take a lot of compounds in already. So you have a huge cocktail cocktail and some of them will obviously do exactly the same as your curcumin or your quercetin or whatever do, 

[00:36:41] JAMES: you know?

[00:36:41] JAMES: I mean, every day I'm eating orange, grapefruit, blueberry, raspberry, banana, apple, a green supplement, several different types of vegetable, artichoke, pepper. Sometimes broccoli, asparagus, everyday. Mushrooms, everyday, yeah, everyday. One of the perks, that [00:37:00] entire biotics, I'll have to say, and if any of you are listening, this is not a critique.

[00:37:07] JAMES: Not that many people take up all the perks, I have to say. So we have the fresh pest, green juice, we have, we had for a while, greens powder, we have unlimited fruit and veg, so it's all there. And I just kind of snack, eat a lot of nuts as well. Um, so maybe I don't need the quercetin every day. So I'm going to think about that carefully.

[00:37:28] JAMES: And, uh, but just, just to push back a little bit, I suppose, because that's my job as the host. Could you argue that we understand biology now better than we ever have done, and it may be advantageous to get a higher concentration of something than you'd typically be able to get through diet? Or is it always going to be about the body's evolved, in tandem with availability of food and quote unquote normality and the optimal strategy for your health is to try and live [00:38:00] almost like a hunter gatherer in some respects.

[00:38:04] PETRA: I think that the second is, is my, my thinking or my, I think I would call it philosophy. I'm not saying as a scientist now, I could tell you it's definitely you should do this and not that. I'm not sure, you know, but just from the philosophy, from the concept, it makes sense to me to say, well, you know, kind of what is normal for us from an evolutionary perspective.

[00:38:29] PETRA: Yeah. Yeah. How our bodies evolved with its environment. And then we can push that a bit, I think, you know, but in the bigger scheme of things, for me personally, And that's all I'm aspiring to as well. I'm not, I'm not one of these people who want to live 200 years, you know. I think it's, I'm quite content with the idea that we all have a limited time span.

[00:38:51] PETRA: I may change my mind when I'm 80 or if I make it to 80, I don't know. You know what I mean? You 80 and go, 

[00:38:56] JAMES: James, give me the protocol for breathing and the ice bath. Too late, too late. I'm going 

[00:38:59] PETRA: to go to the next level. [00:39:00] Too late, Petra. You should have started 

[00:39:02] JAMES: when you were. But that's my philosophy. My philosophy is the sooner you start, But the longer, so there's lifespan, which is I was born and I die, delta lifespan.

[00:39:13] JAMES: Then there's healthspan, which is whatever proportion of the delta of your lifespan you're actually healthy. And healthy is individual. So I know guys who, who want to just be as muscly as possible and you wouldn't believe the extremes. Oh, I know. They're injecting themselves with insulin. Yeah. Growth hormone.

[00:39:36] JAMES: and a cocktail of synthetic and natural hormones every day. And I've had a couple on the podcast, actually, well, one guy on the podcast who's brilliant. And he will say things like, well, actually, there's only one week of the whole year where I actually feel good. I'm like, so what? And it's because for six months of the year, he's force feeding himself.[00:40:00] 

[00:40:01] JAMES: And for six months of the year, he's starving himself. There's a, there's a week in between. And I was like, that's really weird, but that's what he wants to do. But I think what you're describing is I just want to live a healthy, happy life and I don't need to be a hundred, 150 to a hundred. 

[00:40:16] PETRA: Yeah. Yeah. So in terms of lifespan, I'm not too worried to make a, you know, become the oldest, oldest lady in Britain in so many decades.

[00:40:25] PETRA: Healthspan, I do want to stay healthy as much as possible, but also to be honest, I'm worried about, as we talked already about. What harm could I do because I'm ignorant to certain things? But also how important is it really? I know some people who lived. very unhealthy lives and made it to 90 or 100. I know some other people who are super healthy, slim, everything like this.

[00:40:50] PETRA: Every box is ticked and they still ended up as early onset dementia in their early 50s. You see these 

[00:40:56] JAMES: videos of Yeah. So what's the secret? Yeah. 

[00:40:59] PETRA: [00:41:00] My granny smoked into her way, way into her seventies and she died in her late eighties. She was smoking probably two packets of cigarettes. Yeah. So, you know, there's obviously so many facets.

[00:41:13] PETRA: It's our genetics as well and all sorts of things coming together. And for me personally, I'm not putting this either life span or health span over everything else. I want to have fun as well. I do sometimes drink too much and I sometimes do whatever I like and don't get my sleep and all this because I also have learned I think over recent years that my psychological state has a real impact on my physiology.

[00:41:37] PETRA: So I think almost being happy and not too stressed maybe about having taken all my supplements today will also keep you healthy because I do think that, that. Happiness is half the battle in staying healthy. And you know, I have definitely had sort of physical effects from stress, you know, and they have [00:42:00] resolved with the pandemic.

[00:42:01] PETRA: Because suddenly the whole work pattern had changed, you know, and that's a, just one person making an observation. But I think I have learned for myself how So your 

[00:42:10] JAMES: stress levels are better now 

[00:42:11] PETRA: than they've been in the past? Yeah, so I had constant stomach problems, constant. You know, I've been actually on a Meprizole for like six months, and I saw it in the end through the GP, that's all they were going to offering me.

[00:42:20] PETRA: I said, it didn't even help that much, so thanks for that. It was all stress. And then, uh, being able to work from home and I, I have no problems with my colleagues, all fine, but the work environment, you know, shared offices and all this, I'm, I'm one of these strangely, very, very easily, um, distracted people, you know, I can't shut off.

[00:42:40] PETRA: I was really stressed out and, um, yeah. And it took, it took like a year or two. And suddenly one day I realized this is the first time in years, you know, and I had. I haven't had any stomach tweaks and I can't go out for meals in the evening anymore. I couldn't go to a restaurant or anything. I was, you know, my stomach was completely done in.

[00:42:59] PETRA: I [00:43:00] really expected that I would end up with an ulcer or maybe I had, I was on the, on the way to it. And it's completely resolved. Wow. And I'm pretty sure it was due to one very stressful aspect of my work having been taken out on a pretty much permanent basis. Yeah. And I found that. Are you still working from home now or are you back in the office?

[00:43:20] PETRA: I'm mostly working from home. Luckily, my employer lets me do that. So yeah. And you know, I'm, I walk 20 minutes. So I go for all meetings and everything and do everything in person, but I can actually not sit. in my home office and concentrate and not be distracted anymore. So it made a huge difference to me.

[00:43:37] JAMES: That's really interesting. I'm trying to get my people back to the office, but again, you've made me reframe my perspective a little bit because, you know, I think, I think when you're the CEO, you're, you're, well, first of all, you stress all the time. And there's a number of different reasons for that. One, you're accountable for everything.

[00:43:57] JAMES: Two, the buck stops with you [00:44:00] in line with the first thing. But any delay or any issue, you know, you're going to have to report it and take the hit. And when it's going well, it's the best job in the world. It's the best job in the world, full stop. But one of the other things that people don't realize is you're actually the kind of epicenter or the peak of all the problems within the company, which filter up and escalate.

[00:44:21] JAMES: So essentially at any given time, have the summation of all the worst problems in the company every day. That's really stressful, right? And one of the defaults I think when you're CEO and you're stressed is, well, where, where is everybody? You know, they're not in the office. So maybe I need to reconsider that a little bit as well.

[00:44:40] JAMES: What you've said is very profound. It's, it's essentially working from home has impacted your health in a positive way. And that's probably improved your work output as well. Almost certainly. Right now on the subject of your work, cause we've talked about supplements and health and everything, which is great.

[00:44:56] JAMES: Cause we like to cover that in the podcast. What are [00:45:00] you focused on at the moment? Um, so I do also want to talk about fiber by the way. Cause 

[00:45:06] PETRA: yeah, I was going to talk about fiber. No fiber. Yes, 

[00:45:09] JAMES: yes, yes, 

[00:45:09] PETRA: yes, yes, yes. 

[00:45:11] JAMES: So yeah, my main one question before you go was Harry Flint, your supervisor, or was he a colleague?

[00:45:18] PETRA: No, he was my line manager, I would say. So I, I came to the Raud in a tenure track position. So I worked in his group and worked very closely with him for many years. And I was very lucky, uh, because it was very enjoyable. And I think we were very, um, we were very compatible in our thinking and all this. So, you know, I'm one of these, you know, details, people and all this.

[00:45:43] PETRA: And he's the big ideas, big ideas guy. So I think we worked very well together, you know, and then we would keep each other on the straight and narrow stuff, you know? So 

[00:45:54] JAMES: he came on, uh, he's probably the most prepared person I've ever had on the podcast. Prepared? Yeah. In what way? [00:46:00] He came with like a whole pile of, of notes and things.

[00:46:03] JAMES: Yeah. We should maybe talk about this. And if you listen to the episode, it's quite funny because I would love to have him on again, actually, but he sort of Sometimes it was like, well, I just need to finish this point and to finish off the story. And I just loved that because you could tell he was getting really into it.

[00:46:18] JAMES: And I don't think he'd, I don't think he'd been on a podcast before. So he'd sort of had everything well organized and wanted to tell lots of stories. So I thoroughly enjoyed it. Um, but he'd retired, I think. Just as I was getting started with enterobiotics, he made some recommendations. He, he, he, I think via you actually, said I should speak to Elsa Hart.

[00:46:42] JAMES: That was Harry. So, you know, and I did go speak to Elsa Hart. Um, so back to you and, and, and your work and Fiber. 

[00:46:50] PETRA: So, so yeah, when I came to the Railroad, I worked in Harry's group and, um, that was early 2000s and, uh, he had a project. previous PhD student who had isolated all these [00:47:00] butyrate producing bacteria.

[00:47:01] PETRA: So, there is some of the bacteria in the human large intestine. They make this compound called butyrate, um, and it's health promoting. It's, it's really good for you. It is anti inflammatory. It counteracts. It's cancer in the gut. It gives us energy. It's actually the main energy source for the large intestinal wall.

[00:47:20] PETRA: So it really ensures that the colon wall is working, that it is nice and tight and doesn't have holes in it, that all these toxic things that will be in the lumen can get in. And then also it's taken up. And, uh, together with other compounds, so called short term fatty acids, Um, it also goes into the body and regulates all sorts of different things like glucose metabolism, appetite, and so on and so forth.

[00:47:47] PETRA: So, there had been a lot of interest in it, but very few of the bacteria were known that actually makes this magic compound butyrate. Um, and then the, the strain collection was literally there all being built up and then I came on board and with my [00:48:00] very molecular background, Uh, my main, uh, work area really was to work out the biochemistry behind butyrate metabolism.

[00:48:08] PETRA: We kind of knew how they make it, but we didn't know the details. So that's very much what I worked on in my, maybe the first 10 years or so. And then, now, I'm still interested in these short term fatty acids, but I'm also looking much more on the other side of things. So if you think very broadly about fiber metabolism, fiber being those plant compounds that are not digestible in our upper intestine.

[00:48:34] PETRA: So they reach the colon where they are then fermented by the bacteria. That's a huge gap. group of different types of molecules. And so in my early years, they're all broken down to sugars, essentially, let's say glucose is a very simple sugar molecule. Um, and then in the first years I worked from starting with the sugar and looking what happens then once the bacteria have the sugar and making these Georgian fatty acids.

[00:48:59] PETRA: So I focused on [00:49:00] that metabolism and now, That's obviously part of the whole deal, but I'm much more interested now in all these different types of fiber, both in their chemical composition, but also their physical chemical composition. So um, if you think of fiber, it's, it's mainly carbohydrates, so consisting of monosaccharides or sugars, and there are many different types of sugars, there's glucose, fructose, arabinose, xylose, and so on and so forth, galactose.

[00:49:33] PETRA: And then in the plant, they're linked. in, in different long chain molecules. So the plant cell wall, so of your fruit and vegetables, cereals as well, is made up of these long chains of these sugar molecules, monosaccharides, to make this really rigid cell wall for the plant. And there are many different types of molecules.

[00:49:55] PETRA: There's cellulose, which is just a linear chain of glucose. here. Then there are [00:50:00] arabinozylans, which is arabinose and xylose molecules and so on. Some of them are linear, some of them are branched. How they're bound together, the monosaccharides differ. So it's a huge complexity of different molecules coming in.

[00:50:12] PETRA: And we just don't have the enzymes in our small intestine to turn them into sugars. So this is why they're food for the bacteria, they're passing right through. And then different bacteria contain different enzymes coded in their genomes to break these different. molecules down into their monosaccharides and then the monosaccharides are fermented to trojan fatty acids.

[00:50:33] PETRA: So the most 

[00:50:34] JAMES: basic level then the fibers are complicated sugars, complicated carbohydrates, the most basic level and some complicated carbohydrates we can break down in our upper GI tract. 

[00:50:50] PETRA: Starch. Starch. We can break that down in principle. Um, so starch is another macromolecule that consists of glucose, but it is in a [00:51:00] different bond configuration to cellulose.

[00:51:02] PETRA: So it just is three dimensionally, it's different and it needs different enzymes to break them down into sugar. And we don't have the enzyme for the cellulose bond, but we have it for the starch bond. So principally we can break starch down in the small intestine. But often we don't break all of it down because there's only so much time the food moves through the system and the enzyme is chipping away, but the starch is often it's a storage molecule for plants, so it's often big globules and the enzyme is nipping away at the outside and it's liberating some glucose, but some of that big molecule is passing through and then it becomes food for the bacteria as well.

[00:51:42] PETRA: And that fraction of the starch, which is passing through is called resistant starch. Which is 

[00:51:48] JAMES: a hot topic right now in the press and so on and so forth. People talk about get your resistance starch. And so, so how do we sort of summarize fiber then before we jump into the details around different types, you know, [00:52:00] for the listener, because everyone here is, well, you need to eat more fiber for your microbiome.

[00:52:05] JAMES: But it sounds like it's a little bit more complicated than that. Maybe you want different types of fiber. So what, what would be the kind of summary then that a lay person could take away from what we know about fiber? 

[00:52:15] PETRA: So. I think what's also in the press a lot is the diversity of different fruit and vegetables.

[00:52:25] PETRA: And that taps very much into the fiber side of things, also the polyphenols and everything else. It's not just about the fiber, but um, A nice mix of different food ingredients gives, gives you the different types of fiber. And different bacteria can consume the different types of fiber. So there's a very complex metabolic network of the microbes in the large intestine.

[00:52:49] PETRA: Some of them can break down starch. Others can maybe nibble a little bit away at the cellulose implant cell walls, yet other ones do other things. So there's these primary degraders that can [00:53:00] attack the macromolecules and break them down into smaller units, and then there's a complex web of other bacteria that then cross feed from that.

[00:53:08] PETRA: So if you take a wide variety of fiber, you're more likely to stimulate many bacteria, keep a nice diverse group of cells. ecosystem down there. And that applies to ecology generally, not just in the gut, but in general, a more diverse ecosystem tends to be a more resilient ecosystem. So if you compare, you know, a monoculture in a field, if there's one pest coming in, it can wipe them all out.

[00:53:32] PETRA: If you have a very diverse ecosystem, like a forest or something, it's much harder for a pest coming in and wiping out the forest. So the analogy broadly probably holds for the microbes in the large intestine as well. So, you know, um, there has been a while in the media, I think is the, the, what's happening now in, in the television programs has got much better.

[00:53:55] PETRA: But I remember one program about 10, 15 years ago, where it [00:54:00] was all about how do you improve your diet? And this was people eating a very fiber poor diet. And then the presenter was just, it's very simple. You know, you just sprinkle some of this white powder and everything will be fine. And that was inulin or resistance starch or something.

[00:54:13] PETRA: And, you know, so the message was given, you can eat. your burgers or whatever. And then you just sprinkle something on top. I don't think it's that good because these tend to be refined. It's just one type of molecule that goes down there. And once it reaches the start of the colon, it's so fermentable.

[00:54:33] PETRA: It's just, there's an explosion of bacterial activity. It's maybe quite okay in the proximal colon, but you know, the stuff in the colon is passing around for quite a long time. Um, and then. It will, there will not be much to eat for the microbes further down. They can't make their health promoting butyrate and short term fatty acids.

[00:54:52] PETRA: So it's not a good idea. And also obviously if you use masses of one type of fiber rather than a nice fiber mix, you [00:55:00] don't preserve the, uh, the diversity. What 

[00:55:02] JAMES: about the difference between soluble and insoluble fiber? What are the different ways of classifying fiber for the listener to, to learn from?

[00:55:09] PETRA: Yeah, so there is soluble fiber where the molecules basically get solubilized into the water that's in the system as well. And then there's insoluble fiber. And they both play a role. Again, there will be different microbes that can use different types of fiber. Um, so you want a mix of both of them. Some of the soluble fiber also have other other effects.

[00:55:31] PETRA: So we should also think about these in terms of health. So fiber can also have water holding capacities. It can change the viscosity of your food. So it may also may make certain foods stay in your stomach for longer because your whole system, your whole digestive system is obviously influenced by the consistency of it as well.

[00:55:52] PETRA: And then there's the insoluble fiber. So some of that insoluble fiber will just pass through it will not all be [00:56:00] degraded. So if you look in a fecal sample, you will find fibrous matter. Um, and again, it can have physical consequences. It can hold water and change viscosity and lead to bulking. So if there's more material in the gut, The gut wall sees there's something there and maybe does more like muscle movement to move the material on.

[00:56:22] PETRA: So there are all sorts of physical factors. But also from the microbial perspective, I think we need to do much more work on that because we don't understand in detail. And that's very much what I'm interested in, the insoluble fiber structure. So the plant cell wall fiber, it's all these different molecules still bound together.

[00:56:42] PETRA: And if you chew a carrot, you will have bits of carrot floating down there, right? Um, and very few in the field have actually done work on this because it's very hard to study. We have all taken from the companies a [00:57:00] purified fiber where we just have one type of molecule NBC, but how bacteria convert that.

[00:57:06] PETRA: But very few of us have really looked at these complex food particles basically. And now in the last 

[00:57:11] JAMES: few years, we have on. 

[00:57:13] PETRA: The microbiome. Yeah. How important is it? So we talked about this white powder, which we know is very purified, goes quickly through. But if you eat, if you don't take any supplements, fiber supplements, but you eat only plants, you know, how big is the effect on your gut bacteria, on your health?

[00:57:32] PETRA: Do we know that? No, we don't know that. That's what I'm saying. Very few of us have worked on this because technically it's much harder to work with this. But yes, as a microbiologist, he won nice. It's clear solutions media. So then when the bacteria multiply, you can do a measurement called optical density.

[00:57:47] PETRA: If it gets cloudy, you know, your bacteria have grown, imagine insoluble fiber, right? It's already cloudy. 

[00:57:54] JAMES: We did some work together in that project. I can't go into all the details because a lot of it's confidential, but we did some work [00:58:00] together on, on complexity of carbohydrate and I'm just, I was reading that before we came in actually.

[00:58:06] JAMES: So what do we know about fiber then and its importance? 

[00:58:10] PETRA: Well, we're currently working on that and other groups now. I would say in the last five to ten years, more and more groups are tackling it. Because like I say, it's technically so much harder to work with a very complex, insoluble material, which is obviously much harder less characterized, but, um, basically we need to understand this better because there are other functions in the microbiota that may really be influenced by this.

[00:58:36] PETRA: So, for example, how well can they persist in the large intestine? You will be aware that there are different microniches in the large intestine. You say there's the lumen, so bacteria that are swimming around. in the soup, essentially. And there's the gut wall where bacteria may be attached. Yeah. But there's another surface.

[00:58:55] PETRA: There are plant fibers. Yeah. Well, if you don't eat any plants, then you won't have very much of [00:59:00] that. But if you, if you just eat a carrot and you've chewed it, you still have fibers. If you look under the microscope in a fiber, in a fecal sample, you will see three dimensional big fat particles. They're much, much bigger than bacterial cells.

[00:59:14] PETRA: Right. And they're essentially. a colonization surface. So in nature, microbes make biofilms. You find them in, you know, in lake sediments and in soils. So where there are surfaces, microbial communities will attach. Some bacteria have adhesion factors and mix limes and all sorts of things and sit on that surface.

[00:59:39] PETRA: So in the gut surfaces, They do that on the gut wall. Some people are going to be 

[00:59:43] JAMES: so freaked out hearing that there's slime in their body. 

[00:59:48] PETRA: What? No, I don't want any. Well, there's quite some slime on your gut wall. 

[00:59:55] JAMES: No, I know. For sure. There's lots of mucus and slime in there. 

[00:59:58] PETRA: Absolutely. Yeah. So, you [01:00:00] know, we, we don't at this moment in time.

[01:00:02] PETRA: really have the scientific evidence in detail, but common sense tells me it makes physiologically a huge difference. If you eat whole foods and have these big surfaces, and then you have these colonies forming and as touched on earlier, the bacteria. cross feed to each other. So there will be some bacteria that even have little, uh, docking domains that can dock onto the cellulose.

[01:00:24] PETRA: They have little protein domains that can latch onto it. Oh, yeah. So they're adapted to attach to cellulose. Yeah, absolutely. So cellulose degraders tend to have carbohydrate binding domains which are specific for cellulose. Starch degraders have carbohydrate binding domains that are specific binding onto starch.

[01:00:41] PETRA: So they need to bind onto this stuff. Yeah. to be physically close enough, you know, and then these bacteria may start breaking down the cellulose and these macromolecules are so big that they need to do all this outside. Yeah, they can't take the cellulose and because it's massive compared to the bacterium, so they break them [01:01:00] down into shorter units, just a few sugars together, and then they consume some of them, but some of it is normally diffusing away.

[01:01:06] PETRA: So another bacterium, may benefit from it. So now, how important is that biofilm structure to facilitate these cross feeding reactions? Because that happens on very small distances. You know, if you're too far away from that cellulose degrader, you're not going to get any, right? So do bacteria have a benefit that can also then say, I can latch onto this biofilm?

[01:01:29] PETRA: Not with that domain because they may not have it, but in another way or form. So we really don't understand this, um, to sufficient detail. And it is hard to study. So we're working on this. Um, both, we have also looked at looking at the carbohydrate composition of different plants. And again, other people have done this.

[01:01:48] PETRA: So, um, you know, your cereals are different from a compositional point from your fruit and vegetables, but then especially within the fruit and vegetables, you have a lot of variety. So we did a [01:02:00] study with a recent PhD student where he took different vegetables. What was it now? I think it was carrot, kale.

[01:02:05] PETRA: apple, beetroot, and beet leaves. I think it was five. And, um, he extracted the plant cell walls from all these different plants. And then we did, in the lab, we did incubations with fecal samples to see, and he characterized what, what molecules, what monosaccharides are actually in there. And what we found, for example, um, there's a component in fiber that's pectin.

[01:02:30] PETRA: And the pectin from the beets were Also found in apples? Yes, yes. It's really found to a degree in most fruit and vegetables, not so much in cereals. And, and we found that the carrot pectin really stimulated Eubacterium erectile, a butyrate producing bacterium. But the beet pectins, and that was both the beet roots and the beet leaves, they stimulated Bacteroides much more.

[01:02:55] PETRA: Interesting. And then we looked at the composition. Do we understand why, you know, molecularly, [01:03:00] cellularly? Well, the thing is, when we looked at the monosaccharides, so the sugar composition of the pectin fraction, it was really high in arabinose in the beets, and it was really high in galactose in the carrot.

[01:03:14] PETRA: So different sugars. Different sugars. Yeah, different sugars. So we expected, obviously, that the composition is somewhat different. Right. But I, they were the two extremes. The other three were sort of in between. Right. But I never expected that the pectin composition would be so different. So that also goes into eat different foods because it will stimulate different foods.

[01:03:33] PETRA: So all of this 

[01:03:34] JAMES: dietary advice, you know, eat your fruit and veg, is, has kind of been consistent in many respects for a long time. You know, eat real foods, eat your five fruit and veg a day. And we've known that this is associated with health benefits. Could it be that? It's having a direct impact on the microbiome because of the carbohydrate and then the impact on the microbiome is having an impact on the wider body, [01:04:00] potentially.

[01:04:00] JAMES: Yeah, absolutely. So then that leads me to the next question, which is how do we optimize our fiber intake? for our microbiome, gut health, and then our own health. What do we need to do? 

[01:04:12] PETRA: Easy question for you to answer. No, I don't think I would answer to that. So for me, going slightly back to where we were earlier as well, I think it is again a mix of, I don't get too stressed about five things.

[01:04:25] PETRA: fruit and veg a day or 30 different plants per week. Or I think these things are useful. I'm not rubbishing them, but I think for the five fruit and veg, we know that it should really be more than that, I think. But we thought better give people something that they can aspire to, because if you tell them eight or 10, they're probably not going to do anything and give up, you know?

[01:04:48] PETRA: So, you know, they're just to help people to, to, to have a target, but the targets are not. always in line with what we as scientists knew should be done. So I think they're all useful. It's [01:05:00] useful for people to say you should try to eat 30. But at the same time, my personal philosophy comes in again. I want to enjoy life as well.

[01:05:07] PETRA: And also I don't want to get so upset, obsessed with something. I don't want to constantly think, oh, is this okay today? Oh, am I eating something unhealthy? And I saw it with my dad, you know, my dad, at a sort of wake up call in his late 50s. And, and since then, he's really quite stressed when he's just eating that cake at a party or something.

[01:05:26] PETRA: And that's a bit of a shame, you should allow yourself to, you know, enjoy because again, my philosophy is maybe Maybe I'm making that up because it's so handy to have that philosophy. It makes me happy. You know, and as long as it's a reason, I think the problem really comes with people eat unhealthy all the time.

[01:05:43] PETRA: Then you have a huge problem. If you generally eat a healthy diet, it's fine. Also again, from a personal perspective, I grew up on an orchard, but I hate a lot of fruit. I can't stand it. I can't stand it. 

[01:05:54] JAMES: But there are people listening to this. I know that they listen because they tell me and they write to me that that are, you [01:06:00] I suppose in some respects like me trying to optimize, get quite geeky and scientific about everything.

[01:06:06] JAMES: And I think that the story on probiotics I think is quite clear. What you can buy at the moment off the shelf is probably not worthwhile if you're healthy. It might be worthwhile if you've got traveler's diarrhea or you've had some antibiotics, just classic examples. Prebiotic side and the polyphenol side is quite interesting because You know, in many respects, polyphenol containing foods are prebiotic because they've got fibers in 

[01:06:30] PETRA: them as well.

[01:06:32] PETRA: Yeah, if it's not a polyphenol supplement, I guess. 

[01:06:34] JAMES: Right. And then prebiotics more generally, they could be useful for some people in a supplement format. But if you eat all your vegetables, then you should be getting prebiotics within the vegetables. Is that quite, is that correct? 

[01:06:45] PETRA: Well, maybe we should talk a little bit on prebiotics and, and, And fiber.

[01:06:51] PETRA: Fiber, yeah. So there is a lot of confusion in this, I find. And I personally, again, you know, I'm not too hung up on what we call it in the end, but there's [01:07:00] also danger that people then call, you know, everything, everything. So you know, like, Or fibrocreobiotic, which is a, Yeah. Not sure. Well, I don't know. I mean, the prebiotic definition is changing, right?

[01:07:10] PETRA: It changed over time, and I'm pretty sure it will change again. So just to summarize, maybe a dietary fiber, as far as I understand, is what I said earlier. It's your plant food that goes through your system and is not digested further up. So strictly speaking, that could also contain some resistant protein.

[01:07:29] PETRA: So we can digest protein in the upper gut, but there could be some going through. I don't think you would class it as dietary fiber because it's dietary fiber. fiber, not protein. Okay. So there's also resistant protein, but in the broadest sense, dietary fiber is not linked to a health effect as such. Yeah, it is just a very simple and clean definition, I think also needs to be three monosaccharides at least.

[01:07:53] PETRA: So a disaccharide that may also go through is currently not classed as a dietary fiber, but we now get into [01:08:00] the nitty gritty and I'm not really interested, it's about the concepts and the understanding, isn't it? So dietary fiber doesn't have to. have a health effect but we know in fact probably all dietary fiber has a health effect in some way or form.

[01:08:13] PETRA: I talked about also the physical effects, the bulking, the water holding capacity and so on. A prebiotic by definition right now needs to have a health outcome in the body and that needs to be proven kind of. And then also I think still one valid but maybe a slightly earlier definition was it had to be selectively fermented by a microbe in the gut.

[01:08:38] PETRA: Yeah. So in 20 years ago, selectively means 20 years ago when there was much less knowledge about the microbiota and its metabolism of dietary fiber and so on. Um, when we very much thought the gut was full of bifida bacteria and not much else. Yeah. Well, I think people thought that before all [01:09:00] like Harry Flynn's and other people's work came up and said, look, there's all these other bacteria here, you know, because when people before molecular techniques mostly plated out fecal samples to see which bacteria are there, they came up with 70 percent bifids because a lot of the other bugs didn't grow on their media under their conditions or it wasn't anaerobic enough or whatever.

[01:09:20] PETRA: So then I think the idea was like inulin is your classic prebiotic stimulates bifidobacteria end of story and you know our group and others then said look it's more complicated guess what they are non bifidobacteria that can also consume inulin. So that selectivity concept was the central concept of prebiotics.

[01:09:39] PETRA: 15 years ago or so. And then there was a lot of pushback and now that's kind of going by the wayside. But I think at present, at least for one of the currently still valid definitions, it says it needs to be fermented. Yeah. Fermented means eaten? Eaten by the bacteria. And for me, fermentation means the bacteria take that fiber, turn it [01:10:00] into the sugar and then ferment the sugar down to these short chain fatty acids.

[01:10:04] PETRA: That's, as fermentation. One 

[01:10:07] JAMES: question. Is the end stage of sugar digestion and processing in microorganisms always short chain fatty acids? 

[01:10:16] PETRA: Uh, it doesn't have to be, but in the gut it mostly is. Okay, got it. Yeah. I think, like I say, there are different organizations out there and different definitions, but I think fermentation is still one tick box as a prebiotic.

[01:10:28] PETRA: It needs to be fermented, and not all dietary fiber is fermented. So the cellulose, for example, or fractions of other ones may not be fermented, but they may still have a health benefit, but you know, it doesn't have to be fermented for that health benefit. On the other hand, I think some people, I wouldn't class polyphenols as prebiotics if we're going by the fermentation definition.

[01:10:49] PETRA: So the fermentable, the fermentation process is really that that sugar is the main, or is a major energy source and also building blocks for the microbe to grew [01:11:00] with. Yeah. So that's its main metabolism. That's where it gets its energy and its cell material from. Whereas what they do with the polyphenols are little side reactions.

[01:11:08] PETRA: They may be involved in that somewhere. Maybe they use them to dump some electrons in the whole process, but they're not the main food source. So in that sense, if you go by the classic prebiotic definition, polyphenols, I think are not, are not prebiotic. So, so in the bigger scheme of things, I'm not too hung up on definitions.

[01:11:27] PETRA: I just, I'm always more interested in thinking about the concepts and the functions and all this, but it's obviously dangerous that people can jump onto definitions and then everything gets messy. Just 

[01:11:36] JAMES: listening to what you said, is it fair to say, as a summary, I hope I've listened correctly, that all prebiotics are fibers, but not all fibers are prebiotic?

[01:11:50] PETRA: Uh, yes, I think you could see it that way, but then you may now find another prebiotic definition somewhere that's maybe not quite in line. But yes, principally speaking, I think for [01:12:00] a food company to say this has a prebiotic in it, you need to have that health certificate. claim and also due to some definitions, at least it needs to be selective, although that becomes less important, it needs to be fermented.

[01:12:12] PETRA: But I think also the scientific field is aware of this and this definition every few years is, is moving with the time. So I think it's just important for people to know this is not written in stone because As we build up the knowledge also, what we, our understanding changes and therefore the definition may change.

[01:12:28] PETRA: So, for example, that selectivity criterion, which was very central, let's say 10 years ago, 15 years ago, now most in the field say, yeah, we know it's not that selective. To me personally, is it that important that it's selective? And I think there is no one definition out where it says it needs to have a health benefit.

[01:12:45] PETRA: So I think in, in one of these organizations has it even taken out completely. So dietary fiber is, is, is basically, is looking at it much more from a physical point of view and a human body physiology point [01:13:00] of view. Where is it ending up in the body? Is it degraded up there or not? Whereas a prebiotic has this whole health claim associated with it.

[01:13:09] PETRA: But often prebiotics are really dietary fiber, but they tend to be extracted. So if you eat an onion, you will eat some fructans. They are part of the natural matrix of the plant, of the onion, but then a company may take the onion and normally take chicory, but you know, chicory is good, right? Chicory has lots of fructans in it as well.

[01:13:31] PETRA: And they extract just the fructans and then you have that prebiotic supplement. where you can put just the fructan on top. And my big research area is, well, can we really say that that fructan is as healthy as eating loads of chicory and onions and wheat and whatever else? So I think I try to find the scientific, or to gather the scientific evidence together with many other researchers to convince people to say, don't just sprinkle some white stuff on your food, have a white [01:14:00] variety.

[01:14:01] PETRA: And are we there yet? 

[01:14:01] JAMES: Is the evidence base strong enough to say, look, You can buy aniline powder, you can buy pectin powder, you can buy chicory root extract. 

[01:14:10] PETRA: So what you could do, I think the consensus now is very much don't just eat tons of fructans and nothing else. I think the concept, the consensus is there.

[01:14:20] PETRA: It should be a variety of different fibers, whether it's okay to make that up by now having a new white powder that actually contains 10 different things or you want that whole food. I don't think we have enough hard evidence, but my gut feeling tells me, take the whole foods because again, you have, You have the micronutrients, you have the polyphenols.

[01:14:41] PETRA: Yes. You have the food matrix and that's something that we can maybe talk about a little bit more. We touched on the biofilms and all this. How important is that? And then, you know, we come to the next level of Should it be raw or cooked? Should it be a fine flour? Or [01:15:00] should, you know, should you grate things finely?

[01:15:03] PETRA: Should you eat them as raw, that you get big particles in as much as you can? For your grains, whole grains, as in ideally not into flour, well, they may just go through. It may not be the best thing, you know. We started to unpack a bit of that then. Yeah, so what I'm saying 

[01:15:20] JAMES: is What about cooking? Cooking 

[01:15:22] PETRA: versus raw?

[01:15:23] PETRA: Well, I think, again, from my common sense perspective, I quite like a raw carrot, but I would also not take, you know, say no to a cooked carrot. I think a bit of both is probably good. Because, so, going back to the carrots, if you chew a raw carrot, and again, I'm not a food structure specialist, that's from my reading only, but I understand the raw material, and you can get that feel when you bite into it, you break open the plant cell.

[01:15:52] PETRA: Yeah, so there will obviously be particles where there's intact plant cells, but wherever you have the break points, you know, big crack [01:16:00] and the cells literally come apart. So all that material that's inside the cell flows out, obviously. Could be good stuff. Could be good stuff. Maybe that's what would get rid, you get rid of when you cook something and throw away the water later on.

[01:16:14] PETRA: So that's one thing. Also, the fiber structure is then already different. When you cook a carrot, that pectin we talked about earlier is dissolved. That disappears. You may end up eating it still if you keep the juices, if you cook it in a stir fry and the pectin may still be in there, but it's now physically a totally different structure, right?

[01:16:35] PETRA: So, we don't understand that and several of us are now working on this and we're using all sorts of different things. I'm trying to set up microscopy techniques so that I can look at the fiber structure and the bacteria on top and all that sort of stuff, you know? How much does it really matter? So, but my, my knowledge tells me it must have an impact, whether it's a small impact that doesn't really matter or whether it's a huge [01:17:00] impact.

[01:17:00] PETRA: I can't really tell you at this moment in time, but we're working on this. We're looking at and other labs do this. If you work with flowers, you know, like grain flowers, should it be coarse? Should it be fine? Maybe a mix of everything? You know, what is the size of the uh, The flower particle, the surface, that's something I'm working on, you know, the, the surface, depending on how you grind your flower, you could have a really closed, dense surface, which the bacteria may find really hard to attach to, or you maybe have an open, fluffy surface, which is a much better colonization site for the microbes.

[01:17:35] PETRA: Does that affect how these biofilms are forming? And we're really only at the start of this. We don't know enough about it. So my, my hypothesis is Variety. Yeah. Big and small and cooked and raw and all this, it again gives you the diversity that we already talked about in chemical, um, terms. It makes sense chemically that you want the different types of monocytes, [01:18:00] monosaccharides, the different types of bonds.

[01:18:01] PETRA: So it would also make sense on a physicochemical and food processing point of view to have a variety because probably different ones are good for different bacteria. So, 

[01:18:13] JAMES: where does all of this go then in 5 or 10 years or 20 years or 50 years? You know, if you're starting to understand the impact of cooking versus not cooking and complex carbohydrates and mixes of different fibers, where do we go?

[01:18:28] PETRA: I think ultimately, I think, We need to look at all these different things together, and I even want to throw back in sort of my likes and dislikes. You know, I'm not allergic to anything, but I, I really can't stand some fruit. I love berries. I would eat, eat berries every day. And then I can grade fruit into the sort of love it to absolutely hate it.

[01:18:50] PETRA: And it's been like this all my life. What interest? Well, the story goes, I couldn't walk or talk and I was refusing to get any banana stuffed into me. Oh, [01:19:00] really? Bananas. Oh, the smell. Apples can't really stand them. You know, there's a story. I once came to work when I was a PhD student in Germany and we walked along a long corridor and another long corridor and through three doors and all this.

[01:19:14] PETRA: So I could smell. Like from the very start coming into the building. So I walk into the lab and say to my mate, you've been eating 

[01:19:22] JAMES: an apple, haven't you? Wow. He 

[01:19:25] PETRA: said, yes, but that was half an hour ago. So, you know, I've tried all foods that I don't like as an adult again. And I, some of them I don't try anymore because I know it is something in my body.

[01:19:41] PETRA: Um, my body says, I really find this revolting, don't eat it, right? And I'm not forcing anything into my body that my body tells me, no, I don't like this because I don't think it's, I don't know what is, I don't know. I had this all my life. And like I said, I grew up on an orchard. I was exposed to this stuff all the time, you know?

[01:19:59] PETRA: So there's a [01:20:00] certain amount of habituation, obviously, some foods you don't like, but if you keep eating them, it's okay, you know, but I think some of them are so extreme. And I wonder, is there actually something in my genome, you know, that tells me maybe for me, it's not good, you know, and also generally, I'm not a very sweet person.

[01:20:16] PETRA: I don't need lots of sweet things and fruit tend to be quite sweet as well. You know, maybe for my whatever glucose metabolism, it's actually not the best thing if I would eat tons of fruit. And, you know, I, I love every vegetable on the planet. So I eat lots of vegetables, you know, so I think people shouldn't be, and as again, only my personal sort of looking at.

[01:20:38] PETRA: Like, everything, my personal philosophy is, if you really dislike something, don't force yourself. If you think you dislike something, but, you know, like, people who eat, drink tea or coffee with loads of sugar, that's normally not a dislike or a like, that's just a habituation. This is a sugar addiction. Yes.[01:21:00] 

[01:21:00] PETRA: Yeah. But you know, there are certain things that you need to habituate yourself, but very quickly your taste receptors obviously change. And I've done all these tests. So I know that in my case, it's really something much more fundamental. You know, so, and I think why should Why should people force themselves to do something that probably, again, psychologically is not good for them?

[01:21:18] PETRA: If you, if you eat something you find disgusting all the time because you think it's good for you, it can't be good for you, right? So, so I think, yes, variety, but don't stress about every last, you know, you need to have all the different vegetables and fruits on the planet. I don't really think that matters.

[01:21:36] JAMES: Translational aspects of your work, are you going to create new products, new dietary recommendations? Like where do you see it all going and fitting together with 

[01:21:44] PETRA: regards to the future? Yeah, so I, I do like the fundamental knowledge aspects, but obviously, yeah, and also working in the Raoult Institute, we're very much working with the food industry, for example, to get to this next generation of products, you know, if we're [01:22:00] saying, for example, we do want to create prebiotics or dietary fiber ingredients that are good Working for people, I also think we shouldn't be religious about, you know, the only way to go is that full, um, plant based diet.

[01:22:14] PETRA: I think it's also unrealistic. Let's see where the world is going. So I'm, you know, I think it's okay if people really struggle with it. Then we should find these new products. Um, and the RAU does a lot of this. I'm maybe not that involved with it personally very much. But, you know, have your burger, but put some plant based material in to make it more healthy and, and stuff like this.

[01:22:37] PETRA: But I think where we're, where we're ultimately as the whole research community need to go, we need to put all these different aspects together. You know, it is not just the microbiome. It's not just the diet. It's not just your genetics or your immune system, which obviously is primed by your genetics.

[01:22:53] PETRA: It's the whole thing together. And every of these systems is so complex. And [01:23:00] I don't think we're going to be there in five years, but yes, personalization. And you know, it's exciting, these studies where, you know, people now run around with glucose. monitors, and everybody's reacting totally differently. And the microbiome definitely seems to play a role in this.

[01:23:13] PETRA: But I think, again, host genetics will as well, and probably the state you're in that day, you know, as well, obviously, you know, what have you done yesterday, and all that sort of thing. But I think that's really exciting that everything is coming together now and Over the last 10 15 years there has been such an explosion in methodology and you know everything's going exponential which is really hard to keep up with sometimes, I don't know how to read all these papers.

[01:23:39] PETRA: How do you keep up with it? I can't. I find it quite overwhelming. Yeah, Alex said the same 

[01:23:43] JAMES: thing, it's not possible anymore. No it's not possible anymore. So what do you do, read the highest impact 

[01:23:47] PETRA: journals? I tend to do my reading now really specifically when I write either my own work up, I then read intensively about it.

[01:23:59] PETRA: I keep [01:24:00] a sort of tab on, uh, you know, I have a search going on PubMed. So I basically, every Monday I get my alerts and I look through this for 10, 15 minutes and everything that I think, Ooh, this could be, if it's super, super important, I will download the paper right away. Yeah. The, why is it just. put the abstract into a Word file and then I have a searchable database.

[01:24:20] PETRA: So then I go back, you know, if I write, have an invitation to write a review, I can go back to that and through the Word file very easily dig out those in the last year or two that came that are relevant and obviously I use databases, but it's a bit of everything, you know, I use the databases always to see what's going on.

[01:24:38] PETRA: What's new that I have maybe have missed. Do you use AI? No, not yet. Not yet. I don't, I'm, I'm not a big fan, but I'm, I'm sitting on the fence right now, but I've, I'm actually finding it quite. scary from a more societal point of view. And also as a lecturer, teacher, it's, it's very [01:25:00] difficult to do student exams.

[01:25:02] PETRA: And yeah, I've, it's, it's not my, my thing, but I also think it could, for certain things, I think humanity needs it. So I'm not really opposed to it in principle, but for what I'm doing, I don't see the application. And also I, I find it quite scary. What could come out of it? Oh, 

[01:25:21] JAMES: it's so powerful. It's unbelievably powerful.

[01:25:24] JAMES: I think this podcast will become an AI resource in the future. Like, because what we're doing with this podcast, I think is creating the biggest, most in depth library of AI. long form conversations about the microbiome. Right. I don't think it exists anywhere else. So maybe the computers will be able to piece it all together and go, Oh, I will listen to Harry talk about this and pitch talk about that.

[01:25:47] JAMES: And as a result, we've got this new theory. Maybe, I don't know. I don't know. Now, can we just go back a little bit before we wrap up and talk about the hype and [01:26:00] kind of what we know. maybe not for sure, but what we think we know about the microbiome, what we don't know and where the hype's been justified and where it's probably not.

[01:26:08] JAMES: So what's 

[01:26:09] PETRA: your take on all of this? I think we're coming out of the hype now. So like I said, 20 years ago it was a niche area and then it all exploded and suddenly every, every disease could be cured with the microbiome and it was everything. And people jumped to very quick conclusions. Um, and I think now the field has matured so that that's pretty much the past that now I think.

[01:26:30] PETRA: But what is still a big problem which is maybe somewhat related to it is that people just looked at the changes in microbiome, let's say in health compared to a certain disease or the classic one is lean versus obese. And then they saw a change and they immediately jumped onto the conclusion, Oh, well, the bacteria make you fart or something like this.

[01:26:50] PETRA: And that is still happening. And it's still, we haven't managed to get rid of this in, in the research field that people don't have, haven't [01:27:00] mechanistically shown the actual causal relationship and jump to these conclusions. It's got a bit better, but still papers published and you see it in the title, you know, whatever, blah, blah, disease can be cured by this bacterial change.

[01:27:14] PETRA: And then you read the whole paper and you can't find any mechanistic link there. They literally have seen as a change in the microbiota and then they're concluding. that is causing the disease, but of course, and obesity is a good example because, you know, what you eat will affect how much body fat you have and it can also affect the bacteria.

[01:27:32] PETRA: It doesn't necessarily mean a change in both, it's actually cause a link between the two. So, and that, that is infuriating. It still happens a lot, you know, but that also I think contributed to the hype because for a while everybody said, Oh, yeah, bacteria changed and didn't really see what other factors could have changed the bacteria.

[01:27:49] PETRA: Right. side by side with the disease development. 

[01:27:52] JAMES: You must think it is very important because you've been working in the field for a long time. I do, I do. So what do you think then are the kind of tangible [01:28:00] learnings about the microbiome in terms of disease and health that we've taken away? What's, what's real and what's not sort of smoke and 

[01:28:06] PETRA: mirrors?

[01:28:07] PETRA: So I think from, from a healthy person perspective, if you eat very little dietary fiber, you will likely not be as well. and healthy. Both. I think you will probably feel not so good day by day. And I think there's a lot of evidence that shows that very clearly if you eat sort of junk diets all the time, which in Britain is now very, very high, isn't it?

[01:28:34] PETRA: Is it over 50 percent of all food eaten is ultra processed? Yes. And takeaways and stuff like this. It's crazy. You know, it's really crazy. So, um, that, that definitely is, is bad news. So you do need to eat that. diet to be really well and then also you may set yourself up for getting cancer down the line or heart disease.

[01:28:58] PETRA: So we definitely you will [01:29:00] preserve your healthiness and your well being. much more. And there may be some extremes. You talked about Magrani who was smoking heavily and all this. Some people probably get away with a lot of bad diet lifestyle. Same as alcohol. Some people can drink all their life and never get that liver cirrhosis and others hardly any.

[01:29:19] PETRA: So it is very personalized. And again, personalized thing obviously will come much more now in the future that we understand all this much better. So it's the whole system we need to look at. Yes, if you want to stay healthy and well, eat a varied, mostly plant based diet, I would say. I personally am not a vegetarian or vegan.

[01:29:40] PETRA: Again, my philosophy is we weren't evolved, and I don't want to take supplements because I'm worried about not getting enough B12. So I eat meat maybe once a week or something like this, um, and I'm not fussed about whatever if I'm invited or something. I eat pretty much what's been given to me, but mostly I live off plants [01:30:00] and good plants and brown bread or, you know, whole wheat bread and all that sort of stuff.

[01:30:05] PETRA: Um, but I'm not religious about any of these things because again, for me personally, with my personality, I think it would stress me all too much to get too absorbed in every, having it absolutely perfect because I think in the bigger scheme of things. It's not going to make a huge difference. If it shapes five days of my life, because I've sometimes let my hair down or don't worry about it too much, I think that's fine, you know, so that's my philosophy.

[01:30:27] PETRA: If obviously, if you have a disease, then microbiome could have a huge effect. You know, that's a whole different ballgame. 

[01:30:34] JAMES: Now, as we kind of wrap up, are there any sort of key messages, learnings, statements that you think might be helpful for the listeners? You know, in terms of the work that you're doing, fiber, prebiotics, probiotics, polyphenols.

[01:30:48] JAMES: We've talked about the hype and I think that's really helpful. We've talked about the diet, you know, eat a variety of mainly plants. Yep. Is there anything else you think might be quite impactful? 

[01:30:59] PETRA: I think we [01:31:00] probably covered it all. But yeah, I would say, you know, eat a healthy diet, a varied diet, mostly plants.

[01:31:06] PETRA: Don't stress about it too much. But yeah, don't let your hair down every day either. I think if, if you are feeling well and you're eating well, there's no need for, for pre or probiotics. Also supplements. We touched on that earlier. I'm not I try to limit my supplements because I'm worried about potentially overdosing and we don't always, I don't know whether enough studies have always been made.

[01:31:33] PETRA: At the same time, I do take supplements that I think I'm probably lacking in. Vitamin D, probably everybody should. I take the lowest dose and only vitamin D, not multi, this and that and the other. And again, for somebody like me who doesn't like fish very much, I think fish oils are good too. Help me with the old arthritis and all this.

[01:31:52] PETRA: So, yeah, you know, there may be supplements that for you personally with little things you have work out well. But I'm, I'm not [01:32:00] thinking that, sorry James, that you, that it's maybe the best thing for your health to pop the pills like hell because you think more is always better. But I may be wrong, you know, we'll see, we'll talk again.

[01:32:14] JAMES: We shall see. We'll talk again. I don't think we 

[01:32:17] PETRA: need to compare telomeres at some stage. 

[01:32:19] JAMES: We could do that. That'd be interesting. I don't think you've actually aged at all since we first met. Oh, you're not looking very closely. I think that's maybe a result of this plant based diet. I, however, have aged because I saw Oh, you're looking very well, thank you.

[01:32:31] JAMES: It is actually my birthday today. Yes, 

[01:32:33] PETRA: I forgot that. Happy birthday. And 

[01:32:37] JAMES: I can, I, I am aging. There's some grey coming in, but I'm working really hard on staying as fit and healthy as I can. And I do believe in the microbiome. Fundamentally. Me too. 

[01:32:46] PETRA: Me too. Absolutely. But as a part of the whole system, right?

[01:32:49] PETRA: I'm not one of these religious, microbiome is everything and nothing else matters. And I think from my personal experience, also looking around my family, genetics can be so [01:33:00] important. And like I have in my one family, I have the two extremes, you know, 

[01:33:05] JAMES: so we can't change, we can change our epigenetics, we can change our microbiome, which interacts with our genome.

[01:33:11] JAMES: Well, 

[01:33:11] PETRA: we will be able to change our genome. And, you know, that's also so exciting that. All the fields are maturing, you know, I mean, when, when a human genome came out and then there's this big like, and now, and nothing happens for years and now we're really reaping the benefits. So I think on all aspects, we're going to see if humanity is not messing everything up big time.

[01:33:32] PETRA: You know, we are, I know, I know. What I'm saying is if you, if we get the seed, the making, so things better. Yeah. Yes. Yeah. Yes, exactly. It's good and not, so, yeah, I, I think that's the nice thing. It's all coming together now, you know, with this whole personalized nutrition, for example, we talked about it for a long time, but I think the building blocks are starting.

[01:33:52] PETRA: Yeah. And we get the tools and technologies and knowledge all coming together that maybe not in five years, but we will in the future [01:34:00] know what is important for which person, for one person, the microbiome, maybe. The one thing that's, that's the main driver of them not being well for another person, it's maybe a gene that's faulty and we may have the tools to repair that or we can give them effective medication to counteract that.

[01:34:16] PETRA: So, you know, it's one aspect of our body. I think it's as important maybe as your liver or something, but you can't say it's just a microbiome or everything else. In that sense, I think, actually, this analogy with, you know, the gut being another organ as in the gut microbiota being another organ is quite a nice one actually it's just more malleable than your liver which is 

[01:34:36] JAMES: nice and that's very exciting yes so on that note we shall conclude wanted to express my gratitude and thanks both for coming on the podcast but also for all the help and support you've given me and the company over the last how many years now long time but as i'm sure you can see we're working very hard And, um, you know, during the early days in particular, [01:35:00] the support that you gave me, because you were actually the first person I spoke to, and laterally others was fundamental and instrumental.

[01:35:08] JAMES: It wouldn't have happened because I didn't have the credibility and you all took a bit of a bet sitting on this advisory board of this crazy student. So thank you very much. And we're getting closer every day to an approved drug for patients. Great. That's 

[01:35:21] PETRA: super exciting. It is. Well, thank you very much for inviting me.

[01:35:24] PETRA: It was a pleasure. Pleasure. And I have to say, I enjoyed watching your journey from start to, well, where we are now. So yeah. Thank you. Very well done. And I'm very excited for how things are 

[01:35:34] JAMES: going. Thank you, Petra. Much appreciated.

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