A Transit System for Bugs - EWTS #025

Joe: Hello and welcome to Enough with the Science. It's the last episode of Season 2. I can't believe we're here already. I'm Joe.

Senan: And I am Senan. Can you believe this is our 25th episode?

Joe: And I'm sure our listeners have listened to every single one and enjoyed them as much as we have enjoyed making them.

Senan: Yep, and I haven't listened to even one. [laughter]

Joe: That's because they're all coming from your head. It's actually better for you not to go back. [laughter] You just got to keep moving forward.

Senan: Because I listened to one or two actually and I'm there saying, "I didn't really say that. I couldn't have said that, could I?"

Joe: Yeah. Well, now the listeners get to be as surprised as you are.

Senan: [laughter]

Joe: So, today we're talking…

Senan: Anyway, we have some surprises.

Joe: Have we some surprises? Okay, here he goes. He's written this down.

Senan: And these are the surprising things that are taking place under your tummy; in your gut. The gut microbiome and the mysteries and wonders, because we have discovered it's responsible for some wonderful things.

Joe: An obsession of males over 50; the male gut. Just…

Senan: Yeah, it's kind of become a trendy thing to be obsessed with, isn't it?

Joe: What does the word "microbiome" even mean?

Senan: So, it's kind of a closed little ecosystem of microbes. Microbes are those tiny, mostly single-celled things like bacteria, viruses, and fungi.

Joe: That's good; our legal team is going to pull you on that. They're going to pull you on that like it's mostly single-celled. Could be, like, one or two of them could be more than one [laughter] but just in case, just in case they don't pull us up.

Senan: Yeah, we do need to stay just ambiguous enough that nobody can sue us. [laughter]

Joe: I think we're way past; we're way past suing now.

Senan: Also, there's some ancient gizmo in there called Archaea; some really ancient form of life, another single-celled thing. They're not bacteria, they're not viruses, they're not fungi; they're Archaea. I know nothing about them, so we're going to move swiftly along.

Joe: We're going to do an episode about them at some stage in the future.

Senan: [laughter] So for a long time, after they were discovered maybe 150 years ago or whatever, it was assumed that they were just bad germs. All these bugs, all these things we couldn't see; you could only see them under a microscope. Gradually, an acceptance or a realisation came about that they were causing disease, and then the assumption was made that all of them are bad.

Joe: But obviously the first ones that they discovered weren't from the biome; they were outside in the world, yeah?

Senan: Oh, probably, yeah. But back then there wasn't really an understanding of evolution, at least a thorough understanding like we have now, and it wasn't realised that they are actually; or their antecedents are the foundations of all life on Earth. So, those microbes are the first things that developed before any more complicated life developed on Earth.

Senan: Now, obviously we have descended from them, and the current microbes that are in the environment today have descended from them. It's not that the ones that originally developed are still around.

Joe: So the microbes that we have in our gut are kind of slackers; they didn't bother evolving very far.

Senan: Well, I don't know; there's a lot of complexity in microbes. Like, they're able to communicate with each other; mightn't be intelligence, but they are able to send each other chemical signals, and they're able to act together cohesively to do things.

Joe: Can they build, Senan, sandcastles?

Senan: I'd say, you know, a bit like the monkeys and the typewriters and the works of Shakespeare; if you got enough of them on a big enough beach, sooner or later you'd get a sandcastle. [laughter]

Joe: This is our last podcast [laughter] because no one is ever going to take Senan seriously again.

Senan: So, microbiome, microbes; where do we get it from? We humans, that is. So, obviously, most of us anyway, develop as a fetus in the womb…

Joe: Again, our legal team has warned us. [laughter]

Senan: …other than the ones who are maybe found under a cabbage. But that environment in the womb is amazingly not sterile. Somehow, some microbes manage to get in there; but it's a very limited set of microbes in the womb. So, just before we're born, we kind of have this very limited microbiome that's nowhere near as complicated as what we will end up with after we're born.

Senan: So, our first large-scale exposure to bugs that will eventually find their way into our gut microbiome is when we travel through the birth canal; and whatever bugs are present in our mother's birth canal is the ones that we pick up on the way out, if you like. That's our initial…

Joe: Mammy germs. Mammy germs; seeds.

Senan: Yeah, mammy germs; the initial seeds. And it's interesting, while we're on the subject of infants, human breast milk has a component called oligosaccharides that…

Joe: You've got much better pronouncing that.

Senan: I know. Well, this, folks, you should realise, this is the 18th take of this podcast because of the mess I made of that word in the past. [laughter] The fact is, human infants are incapable of actually, themselves, digesting that component of the breast milk…

Joe: That big word that I'm not going to try a second time.

Senan: …but bacteria; it's food for bacteria. So, it actually helps the fledgling inoculation of a microbiome that infant has picked up when they were being born. It helps that to grow into a healthier, larger number of microbes in their gut.

Joe: So essentially, in breast milk, there's food that's only good for bacteria?

Senan: Bacteria, yeah. So, you'd have to ask evolutionarily; why did that happen? And one would think it's because somehow those bacteria and bugs in our gut are beneficial to us in some way.

Joe: Yeah. I think that's the first time I've ever heard "evolutionarily" used as an adverb.

Senan: Evolutionarily. [laughter] Anyway, and that's only the start. So, toddlers then, they'd be; things they come into contact with in the environment, you know, they're crawling around in the dirt.

Joe: Worms. They love eating worms.

Senan: Yes; playing with pets, whatever food they're eating…

Joe: Is that true? Is that, I don't know, is it that old wives'… like, the best thing to give a child is a puppy?

Senan: Well, I don't know; it depends on whether the child is going to eat it or not, but [laughter]…

Joe: Okay. I don't know what kind of children you had. [laughter]

Senan: But there is a school of thought among scientists that says that households that have dogs tend to have a more diverse microbiome in the people that live in that house.

Joe: And sorry, because I'd heard it, but I just didn't know was there a scientific basis for it.

Senan: I think there is, yeah. Now, whether it's a good thing for small toddlers whose immune system is not currently at the races just yet, that's another matter.

Joe: Okay.

Senan: But roughly around age 3, you have developed a fairly mature microbiome in your gut.

Joe: [laughter] I was just thinking that, like, if there was a listener out there who was actually using this as advice; we have to be so... you were so careful going, "I don't think it's a good idea to give like little kids dogs," just in case someone was listening going, "Oh, the lads in Enough with the Science said it was a good idea to get a dog." [laughter] If you're living your life by the stuff that we're talking about, you have bigger problems [laughter] than getting a dog for your child.

Senan: You do. [laughter]

Joe: Okay, sorry.

Senan: Excuse me for stating the absolute bleeding obvious here. This show is for entertainment purposes only. [laughter]

Joe: Mostly of ours.

Senan: Correct [laughter] because let's face it, we constitute about 30% of the listenership; just the two of us. [laughter]

Senan: Anyhow, of course, it is topped up throughout your life. It's not just that, okay, by age 3, you've got this fine healthy microbiome; but the thing is, throughout your life, everything you eat, every person you meet, every dirty thing you pick up, all contribute to topping up your microbiome, because some of that stuff ends up going into your mouth.

Joe: Right.

Senan: So, yeah, it's a constantly evolving thing; but the numbers are pretty eye-opening actually, in terms of the size of it. The average adult human has about 30 trillion human cells in their body, right?

Joe: Okay. So, if you put them end to end, they'd stretch to…

Senan: …probably Kilkenny, I think.

Joe: Okay.

Senan: Maybe Carlow, if you're…

Joe: Maybe Carlow.

Senan: Anyway, but so that's 30 trillion human cells; but that same average adult has 38 trillion microbial cells in or on his body or her body.

Joe: So that's inside and out?

Senan: Oh, yeah, everywhere, yeah, inside and out.

Joe: So, like, the sheer number of cells alone means you're in the minority, but…

Joe: Essentially, we are filthy. We are filthy, filthy people.

Senan: No, we're actually; all we are is a means for bugs to get around. We're a transport system for bugs.

Joe: Okay. [laughter] That's the nicest thing anyone has ever said about me. [laughter]

Senan: And the numbers are even more bonkers when you start looking at genes. So, a…

Joe: Right, you're going to have to explain that.

Senan: We're not talking about Levi's here, by the way.

Joe: He's going to make that joke every time we say genes; every single time.

Senan: No, occasionally I say Wrangler; occasionally. [laughter]

Senan: Anyway, a gene is the bunch of DNA that makes one protein. It's not just one little piece of DNA; it's like several bits of DNA that act together to make… anyway, we humans have roughly 20,000 genes in our DNA. Because of the huge diversity of different microbe species that are in your microbiome, there's anywhere between 2 and 10 million separate microbial genes in your system.

Joe: That's actually a huge difference, isn't it?

Senan: It's a massive difference, yeah.

Joe: No, but I mean it's a massive difference, like, between 2 and 10 million. Not only is it a massive difference between our genes and their genes, but 2 and 10 million is… it's not like 2 or 3.

Senan: Well, some people have a huge diversity of different species of bugs in their system versus others. So, that's kind of where that difference is arising from. One person might have literally a thousand different bugs in their tummy, and another person might only have 200 or 300. So, you know, that's where that kind of arises from.

Senan: And while we're on the subject of numbers, [laughter] here's a slightly icky bit. The proportion of your poo that is… [laughter] not leftover digested food; about 30% of your poo is microbes, either dead or living ones that are being shed…

Joe: That have been freed. Freed!

Senan: …into the environment.

Joe: On day release. [laughter]

Senan: And of course, that doesn't mean the number of bugs in your gut is being depleted as a result, because they are reproducing in there the whole time. You're providing them with warmth and food; why wouldn't they?

Joe: I am going to stop thinking about this information as soon as this podcast is finished. I'm never going to think about it again.

Senan: Initially, as I said earlier, science thought that all bugs were bad, because they kind of realised that some bugs were causing disease and they assumed all bugs were bad. Antibiotics were developed and they started to be used extensively, because it was believed that by using them to kill off these bugs, it would help us to stay healthy.

Senan: But an interesting revelation happened in developed countries. As antibiotics started to be used in a very widespread way, the rate of certain kinds of diseases; allergies, asthma, autoimmune diseases, those diseases went way up. Far more of those diseases started happening in these developed countries that were using antibiotics.

Senan: And of course, when you take an antibiotic, it's like a scorched-earth situation. It doesn't just kill one bug that you're trying to kill; it probably kills the majority of the bugs that are in your gut, of all the different species.

Joe: Destroying your microbiome essentially; you're nuking…

Senan: Yeah, or nuking it. Now, there is some evidence to suggest that there are parts of your gut where bits of it can hide, and when the storm is gone, they can re-emerge and help to recolonise your gut. But, nevertheless, you are wiping out a huge amount of your microbiome by taking antibiotics, even though you're trying to target one particular bug that's making you sick.

Senan: The conclusion, I suppose, that you can draw from that realisation… well, that was kind of what helped scientists to realise that maybe some of these bugs are actually useful. But the conclusion, I suppose, is that there are elements of your microbiome that have some kind of a role in helping to prevent those diseases that started to become more common when antibiotics were being used. So, it was an interesting, eye-opening moment for science.

Senan: But the real, I suppose, epiphany about how diverse this microbiome was and how many different roles it played only came about when we developed advanced gene-sequencing techniques. So, in other words, if you take a sample of any organism, be it human tissue or bacteria or whatever, you can run it through a sequencer machine and actually get a printout, as it were, of the DNA for that organism, right?

Joe: Right.

Senan: Prior to that, if you wanted to figure out what bacteria were present in a particular sample you'd got, you put that sample into a Petri dish; which is a glass dish with agar gel in the bottom of it, which is like a sugary substance, and you incubated it because the bugs usually like to be in a warm environment. You come back a week later and you've got these spots of individual bugs that have grown on it, and you now have enough of them to make an analysis of what each one is, right?

Joe: Right.

Joe: Got you.

Senan: But, the problem with that is that 95%—this was only discovered later on—95% of the constituents of our gut microbiome are anaerobic bacteria. In other words, they're bacteria that can only survive in a zero-oxygen environment. So, once you took them out of the gut and exposed them to oxygen in the laboratory, they died off.

Senan: So, we never saw them; we didn't know they were there. They were invisible to us. And it was only when we actually started to use DNA sequencing about 20 years ago to analyse what DNA was present in poo samples, that we discovered there was this huge diversity of other organisms in there.

Joe: I imagine they must have thought the machine was broken for a while, [laughter] going, "No, that can't be right. That's just not... that's not real."

Senan: Your poo broke the machine! [laughter] You owe us a million. [laughter]

Senan: And then, this huge project. When they started to get a glimpse into what might be in there, in America, they set up this enormous project; the 2007 Human Microbiome Project. They spent over 150 million to sequence the microbiome genes in not just the gut, but various other parts of the human body in healthy people. So, they wanted a map of what does the microbiome—in other words, the collection of microbes in a healthy person—look like?

Joe: Right.

Senan: As a baseline. We can then, once we have that baseline, we can obviously analyse that and make some conclusions, but we can also compare that to a person who has various different diseases, to see how different the microbiome is in those people versus a normal healthy one.

Joe: Yeah.

Senan: So, it was a massive project which to this day, the benefits of it are still being used throughout scientific research. As I said, there's lots of different constituents; you know, it could be over 1,000 different individual species in your gut.

Joe: Now, just because earlier on you said that there's actually quite a variation in the number of individual species between people, is more better?

Senan: Generally, I think more diversity is considered to be better, right?

Joe: Multicultural, if you will.

Senan: Multicultural; multicultural diversity is definitely a benefit in that micro world as well as in the macro world that we live in. We have all these different species in our gut; different bacteria. Some of them are unhealthy ones, ones that have the potential to make us sick, things like E. coli, for example. They are present in a small amount in practically all of us. We carry these things around with us and they don't make us sick, usually, right?

Joe: Right.

Joe: And they don't have a job; they just happen to be there because we stuck our dirty fingers in our mouth at some stage.

Senan: Yeah, as far as we know. I mean, do any of these things have a job? [laughter] Or is it just happenstance that they happen to be doing something that's beneficial to us? Anyway…

Joe: Well, I'm not giving them sentience; I'm not like giving them conscious thought [laughter] but I just thought…

Senan: You heard it here first, folks: we are actually just transport machines for biomes.

Joe: We are indeed. [laughter]

Senan: So, there's a couple of reasons why they don't make us sick, even though we're carrying them around inside us every day; even though sometimes they do make us sick, and we'll come to that in a minute. But, the reason why they generally don't make us sick—there's two reasons. First of all, the lining of your gut is extraordinarily good at preventing bacteria from escaping from your gut into the rest of your body and causing illness, right?

Joe: Right.

Senan: And it's good in two ways. First of all, it has this real thick layer of mucus that they get bogged down in…

Joe: Stuck in.

Senan: …and then underneath that, it's got this really dense, tightly packed layer of cells. I was going to call it skin; it's not exactly skin, but imagine it's the outside layer on your skin, except this is on the inside of the lining of your gut. Those cells are so densely packed together; it's difficult for any bugs to get through. The other thing it's doing is it's constantly shedding the top layer of cells, right?

Joe: Right.

Senan: So, it's growing new ones deeper down that migrate towards the top; and the ones on the top, and some of the mucus, fall away. That means that if some of those bugs are starting to make inroads into getting through that barrier, when the upper layer of cells are cast away, those bugs fall away with them. So…

Joe: That's only one reason, right?

Senan: The other reason is, I suppose, what you'd call competitive pressure. So, remember, you've got maybe a thousand different, or several hundred different, species of microbes in your gut. They're all competing for the same resources; for the food that you're supplying them with every day, and the heat and so on that's available in there to help them grow. Each individual species can only grab so much of the resources for themselves, which means they can only produce so many babies. [laughter]

Joe: Right.

Senan: Your body can cope with even the bad stuff like E. coli and some other bad ones; your body can cope with a certain level of that without getting sick. It's only if it reaches a kind of critical mass; the amount of it that's physically there is enough to make you sick.

Senan: That effectively is what happens when you eat, say, food that's gone off. There's a huge amount, say, chicken that's infected with E. coli, we'll say. There's a huge amount of E. coli in that piece of chicken, because the chicken has gone off and the E. coli has had enough time to rapidly… I was going to say evolve, but…

Joe: Reproduce.

Senan: Reproduce, thank you. [laughter]

Senan: So, you're upsetting the balance, right? By eating that chicken, you now have a much higher proportion of E. coli in your biome than you would otherwise have had; and it's above the critical mass, it's able to garner more resources for itself and crowd out all the other guys, and suddenly you've got loads of it in your system and it's enough to make you sick.

Joe: There you go. Well explained, eventually.

Senan: Yeah, eventually, when I can think of the right words. [laughter] Now, how do scientists actually study this microbiome?

Joe: Rabbits. There's rabbits. There's baby, cute baby rabbits involved.

Senan: Funny enough, it's mice, mostly.

Joe: Okay.

Senan: Rabbits without tall ears and small little things. So, scientists are able to create something called gnotobiotic mice. And, believe it or not, that word starts with the letter G.

Joe: G-M-I-C-E?

Senan: No, gnotobiotic. [laughter] Yeah, the part of my brain that forms language is not firing very well this week. [laughter]

Joe: You've got brain poisoning.

Senan: It's the summer sun that's got to me.

Senan: Anyway, these gnotobiotic mice are germ-free mice; mice that have been somehow bred in a sterile environment, and they've made sure that they don't have a microbiome, basically. And then they can introduce just one specific species of bacteria or whatever into their gut to see what it does.

Senan: That's kind of one of the ways that scientists have been trying to get a hint about how these different things interact in our bodies and what they do for us.

Senan: But more recently, with DNA sequencing that I mentioned earlier, scientists are heavily relying on fecal sampling; basically taking poo and analysing all the DNA that's in there to study things.

Senan: And also analysing, of course, all these different bugs are producing various chemicals; biochemicals, as byproducts of their own activity. A lot of the effects that they have in our system is down to what chemicals they have produced; so, analysis of the chemicals these things are producing is also going on.

Joe: And the interaction between all the chemicals.

Senan: Yeah, it's a hugely complicated situation. Interaction between the different chemicals, and then you've got our own genes and what kind of environment they have created in our body, and so on; it's a really complicated picture.

Senan: That's why it's so hard to draw hard and fast conclusions about things. You will tend to hear scientists, when they talk about this, say, "Such and such a thing tends to happen in this situation," or, "Such and such a thing tends to happen." Because if you take a group of 100 people and you subject them to a particular study, because of the diversity of the genetic makeup of those people, and their eating habits, and their lifestyle habits, and so on, they are all going to react slightly differently to a given set of bugs in their microbiome.

Joe: Right.

Senan: So, it's not a cut-and-dried kind of science.

Joe: So, just one factor. Your microbiome is one factor in many that affects how your body works.

Senan: Yeah, it's one instrument in the orchestra.

Joe: Yeah. And one that just wasn't known about until…

Senan: Yeah, absolutely.

Joe: It's like, "What is that noise?" [laughter] "What is… a piccolo? There's a piccolo over there!" [laughter]

Senan: Anyhow, some really interesting discoveries have been made about what the microbiome can do for us. There are certain groups of plant fibers in our food that we don't have the chemical equipment to break down ourselves. Some elements of our microbiome are essentially starting the digestion process of those fibers for us; they kind of partially digest them to get them to a point where we can then deal with them.

Joe: Right.

Senan: So, that's one thing that it does for us. There is a thing called short-chain fatty acids, which are a crucial component of keeping the mucus layer in our gut healthy—that mucus layer we spoke about a while ago. Those are actually produced by certain species of bacteria; so, it's as if something the bacteria produce is helping to stop those bacteria from getting out of our gut into the rest of our body.

Joe: Okay.

Joe: But obviously it'd be different bacteria; they're not sort of doing it to themselves. It's not the E. coli that's producing the…

Senan: I don't know which ones; maybe it is, I don't know. It could be just one of those happy accidents, you know.

Joe: "We don't want to be successful; we want to get out, but we're going to stop ourselves from getting out." [laughter]

Senan: Other bugs in there are synthesising some vitamins; Vitamin K, and some of the Vitamin B group—there are sub-vitamins in the B group—some of those…

Joe: Vitamin K? Did they just skip a load of letters? [laughter] Did they just go straight to Vitamin K? Let's, let's… no, Vitamin F. I've never heard of Vitamin F.

Senan: I don't know if there's an E, F, G, H, I, J. They went straight to K. I don't know.

Senan: Anyway, these vitamins are not exclusively made for us by bacteria; we get these vitamins directly from our food. But, they are a good secondary source of some of those vitamins, so it's interesting that some of their byproducts are things we directly need to keep our bodies healthy.

Senan: And there's other really interesting stuff, too. One of the ones that's been studied a lot is the difference between people who are overweight and people who are underweight; are there particular common patterns in the population of their microbiome?

Senan: It turns out there are. If you take 100 people who are overweight and 100 people who are underweight and compare their microbiome, you will see certain patterns emerging about what the population of individual microbes is. Of course, there's been some debate about: is it a cause-or-effect thing? In other words, do they have the different stuff in their microbiome because they're thin or fat; or did the stuff in their microbiome help cause them to become thin or fat?

Joe: Right. Okay.

Joe: Chicken and egg.

Senan: Yeah, and there's been some interesting studies. Our friends, the mice, got involved [laughter] where they took some of these germ-free, sterile mice and gave them one or other of the typical population that you find in somebody who is either overweight or underweight. They did observe that those mice tended to get heavier or lighter…

Joe: …as you would expect.

Senan: So, at least there is some element of cause. But there's one really intriguing study done on teenagers. It's a pity that it's only one study, because this sounds very interesting. They took a group of—I'm not sure of the number, but there might have been roughly 100 teenagers involved—and one group was the placebo group that got nothing. The other half got little capsules of dried poo, basically. [laughter]

Senan: I know it sounds absolutely gross.

Joe: Yeah, it does sound absolutely gross.

Senan: …from people who were underweight, or certainly skinny. So, they took typical microbiome samples from people who were skinny their whole lives…

Joe: Skinny people's poo.

Senan: Yes. Dried it, did other things to it to maybe stop it from…

Joe: Maybe taste like chocolate. [laughter]

Senan: …stuck it into a capsule that would not dissolve in your mouth, and made you swallow quickly. But, the thing is, they only got this maybe once a day for a week; so, it was a relatively small dose of it.

Senan: And initially, the first two or three years, they didn't really notice much difference between the two groups; the placebo group and the poo group.

Joe: And did they... I wonder did they have any expectation of the length of the study they were going to have to do? Did they think that they were going to have to follow them up?

Senan: I don't know at the start. But anyway, they did go back to them 10 or 15 years later, and there was a definite difference. The ones who were not in the placebo group, on average, were thinner than the ones who were.

Senan: Look, I have to say "on average," because there's so many other factors involved—like what's your lifestyle, and your diet, and all the rest of it, and your genetic makeup—that not everybody in the non-placebo group was thin, and not everybody in the placebo group was overweight. But, on average, they tended to be thinner. So, it's interesting that a relatively small dose of something when you were a teenager had an effect on your body decades later.

Joe: So, I mean, and obviously the conclusion of that is the biome is much more important in our physical health than we realise?

Senan: Oh, yeah. I mean, it kind of has its finger in a lot of pies, in terms of different aspects of our health that it affects.

Senan: And there's a theory about… the next question is, "How does that mechanism actually work?" If we're all eating roughly the same amount of food, how come some of us get heavier than others? A theory—and it's not proven, it's purely a theory—is that the particular constituents of your microbiome can affect the amount of calories you extract from the food, right?

Joe: Right.

Joe: So that unused calories can be excreted; you're not actually using every last calorie in the food.

Senan: Yeah. So that your microbiome might be regulating the amount of it that's being absorbed. It's a very interesting area that needs more study, because, obviously, if you can take something for a week that's going to have a lifelong or nearly lifelong effect, it's probably a lot more desirable than something that you have to take every day, like the modern… what do they call those drugs; the semaglutide, those things.

Joe: The injections?

Senan: Yes, yeah. That weight-loss stuff. The drugs that were originally developed for diabetes that are now being used for weight loss.

Joe: Ozempic.

Senan: Ozempic and Mounjaro and things like that. You have to keep taking those once you start, because people who take them for like a year lose 3 or 4 kilos or whatever it is, stop taking them; a large percentage of those people a year later have gone back to the weight they were at, yeah.

Joe: So, distasteful as it might be, a week of poo… a week of poo tablets might be just much more…

Senan: And they do what are called fecal transplants now. At the experimental stage, they were doing it in the gross way you might imagine.

Joe: No, because, like, I'm just not letting myself imagine that. A fecal transplant?

Senan: Yeah, well, let's just say the recipient of the transplant was getting it in through the outdoor. [laughter]

Senan: Anyway, one of those antibiotic-resistant bugs that cause havoc in hospitals and, unfortunately, kill lots of people is called C. diff, or C. difficile. Actually, where it's resistant to drug treatment, they've been very successful at treating it with poo transplants from people whose microbiome has a much lower incidence of C. difficile than the sick person has.

Joe: Oh, okay.

Senan: So, it's like they can wipe out the sick person's gut microbiome and then give them a transplant of a relatively small amount of poo from somebody else who doesn't have that bug in them. Their microbiome re-establishes without that bug, and it tends to cure the illness. It's incredible.

Joe: That is incredible. But I think we'll just leave that one. Can we just move along from that one, because I don't want my imagination going with the poo transplants thing?

Senan: Okay, well, that was at the experimental stage. Now they're moving towards dried stuff in capsules; a bit more palatable, as long as you don't think about it. [laughter]

Joe: Oh, okay. That's grand; that's grand. I imagine even for the physicians as well. [laughter]

Senan: And there's kind of been similar hints in research towards things like psychological issues; like, say, people who are depressed—chronically depressed—versus people who tend to be happy a lot. They've done some analysis on different microbiome populations between those two groups, and there are some hints that there are certain populations associated with depression.

Joe: Right.

Joe: And so, like, the poo tablets might work there, too?

Senan: Yeah, now, I think it's very early days with the research there, so I wouldn't like to be raising anybody's false hopes, but, yeah.

Joe: "Just find a really jolly person. Would you do me a favour? Just this little baggie." [laughter]

Senan: So, and the mechanisms there… God knows what the mechanism is there. Like, is it that the bacteria are producing neurochemicals that are getting into your blood and finding their way to your brain; or is it that the bacteria are somehow sending messages up the nervous system to your brain? It's a very broad potential field there to try and figure out what's going on. But it's amazing to think that something that's going on in your tummy is somehow affecting your head.

Joe: Well, and I mean, and the fact that it's bacteria; these little dudes [laughter] are having such a huge effect on your physical and psychological well-being.

Senan: So, we're going to leave you with a few tips of what science says about the best way to maintain a healthy microbiome, right?

Joe: Okay.

Joe: Is Guinness involved in this?

Senan: Something that might end up being Guinness is involved in this. [laughter]

Senan: So, remember that I spoke about that American Gut Project study; they spent 150 million on sequencing all the healthy stuff. They came up with some interesting analysis where they looked at what was associated, in terms of people's lifestyle and dietary habits, with the most diverse gut microbiome. Because, generally speaking, the more diverse your microbiome is—the more different species you have in your gut—that tends to be healthier for you in general, right?

Joe: Right.

Senan: And the greatest predictor they found was that if you ate… they called it the 30-plant rule. Basically, if you ate 30 different types of plants in a week, that level of diversity in your diet was echoed in diversity in your gut microbiome.

Joe: Thirty different plants? Would be like taking the heads of weeds on the way home, just like, "Yes, dandelion, grass."

Senan: Well, if you have a bag of mixed nuts, there's probably five different kinds of nuts in that bag. That's five straight off.

Joe: And then if you have a different bag of nuts, that's another five; there's ten, done. [laughter]

Senan: If they are different types of nuts, yes. [laughter]

Senan: So, that's one. Another one is fermented foods; and this is where your Guinness comes in.

Joe: Woo-hoo! [laughter] I knew it. I knew it.

Senan: Now, whether the adverse effects of alcohol balance out the positive effects…

Joe: Don't take it away! Fermented foods; it's a fermented food.

Senan: Anyway, really, the scientists were thinking of things like kefir, kimchi, sauerkraut, kombucha, and all that.

Joe: Okay.

Senan: And, I suppose, yoghurt.

Senan: Lifestyle, of course. Antibiotics; we should really talk about antibiotics. Now, this is a bit of a hot topic, because people have strong opinions about it and so on. But, it's not that I'm about to discourage people from using antibiotics at all…

Joe: And again, anybody who's listening to this podcast for advice, you deserve what you get. [laughter] Yes, this is an entertainment show. Do not use us as a guide for your life.

Joe: But antibiotics are, essentially, you shouldn't take them unless you absolutely have to.

Senan: Yeah, I mean, if you're seriously ill with something that can be cured by an antibiotic, of course, you need to take it and shouldn't even think twice about that. You should take the medical advice. But, what we should be avoiding doing is unnecessary use of antibiotics. Because it's a real scorched-earth thing; when you take a strong antibiotic, you're essentially nuking your entire microbiome and hoping that it'll re-establish in a healthy way later.

Senan: So, sure, you need them sometimes, but don't take them unless you absolutely need them.

Senan: Stress is another one. Apparently, people who are under stress, the mucus barrier in their gut lining is degraded.

Joe: Right.

Senan: Ultra-processed foods. Foods, essentially, that contain chemical emulsifiers—which are typically found in ultra-processed foods—again, tend to interfere with the gut lining.

Joe: Okay. So, that means the bad bacteria can get in to where they shouldn't go, essentially?

Senan: Yeah, and so you have the potential for the bad bacteria to cause problems in your body.

Senan: And I suppose one of my favourite ones—that's a real broad rule of thumb—is that the plants that you eat should be as close to the state they were in when they came out of the ground as possible.

Joe: Don't wash them! [laughter]

Senan: Well, actually, there is, obviously, the potential for you to get some bad bugs, especially if there's cow poo on them. But leaving that aside, the point is: try not to cook your vegetables until they're mush, right?

Joe: How did any of us survive? I mean, that was the traditional way of cooking vegetables in Ireland for generations.

Senan: It was indeed; it was. God almighty, do you remember the cabbage? [laughter]

Joe: God almighty, do you remember the smell in the house?

Senan: Yeah, I know. [laughter] And that is the end of not only today's show, but also Season 2 and Episode 25.

Joe: Episode 25! So, thank you so much for putting up with us, if you did put up with us. And if you didn't put up with us, well, I hope you put up with us next season.

Senan: Yeah, we'll be back for Season 3 in the autumn, because it is just the start of the summer here in Ireland; the summer lasts about one week in Ireland [laughter] so we'll be back in the autumn when we've had enough sunshine.

Joe: Okay, listen, take care. Thanks for listening.

Senan: Yes, indeed. Goodbye.