Microbial Connections

How growing miniature stomachs can help uncover our evolutionary history with microbes

Episode Summary

How can a microbe responsible for ulcers be either beneficial or harmful to you depending on your genetic background and at what time in life you are infected? And why are fewer Danish children today infected and what does that mean for the future of our health? Associate Professor Sandra Breum Andersen will answer all of these fascinating questions in this episode of Microbial Connections on her field Evolutionary Medicine.

Episode Notes

Your hosts are PhD Christina Lehmkuhl Noer and Professor Tom Gilbert. Sound and recording by Christian Grimes Schmidt from Centre for Online and Blended Learning and editing by Christina Lehmkuhl Noer and Ella Zoe Lattenkamp.

The Center for Evolutionary Hologenomics and this podcast are generously funded by the Danish National Research Foundation.

Episode Transcription

00:00:00 Sandra Breum Andersen

So one of the neat things about Helicobacter is when you do the phylogeny of the bacteria, you can track our movement out of Africa.

00:00:09 Tom Gilbert

Well, hello and welcome to another episode of Microbial Connections, a podcast where my co-host Christina and I talk to experts about the fascinating new research field of holobiont biology, where host organisms and their associated microbes are viewed as one intertwined.

00:00:27 Tom Gilbert

My name is Tom Gilbert.

00:00:29 Christina Lehmkuhl Noer

And hi my name is Christina Noer and we both work at Center for Evolutionary Hologenomics at University of Copenhagen.

00:00:36 Christina Lehmkuhl Noer

And today our guest is our dear colleague, associate Professor Sandra Breum Andersen, also from Center for Evolutionary Hologenomics.

00:00:46 Sandra Breum Andersen

Thank you for having me.

00:00:49 Christina Lehmkuhl Noer

So Sandra, your research field is called evolutionary medicine, which we're very excited to hear about and, we asked you to bring something that represents your research.

00:01:02 Christina Lehmkuhl Noer

What did you bring?

00:01:05 Sandra Breum Andersen

You can maybe hear it but you can't see it, but I brought this plastic dish. It's a 24 well plate. And in each of these wells, we can grow miniature stomachs that we can then expose to microbes and other things and see how they respond.

00:01:25 Tom Gilbert

And these miniature stomachs, these are organoids?

00:01:28 Sandra Breum Andersen

They are organoids, yes.

00:01:30 Christina Lehmkuhl Noer

So how do they? Can you explain like how does such a miniature stomach look like?

00:01:35 Sandra Breum Andersen

Yes, I certainly can.

00:01:38 Sandra Breum Andersen

So in the stomach and the other intestinal tissue, there are stem cells. And when we take the tissue from sacrificed mouse, we can coax these stem cells into growing into stomachs in the lab by giving them a cocktail of growth factors.

00:02:00 Sandra Breum Andersen

They grow into these little spheres and so a round shape, which is the organoid.

00:02:07 Sandra Breum Andersen

The advantage of these is that they still have the different cell types that are found in the stomach, so they resemble the stomach to some degree.

00:02:17 Sandra Breum Andersen

So that means we can avoid using live animals for our experiments.

00:02:23 Tom Gilbert

So they kind of resembled the stomach at the cellular level.

00:02:25 Tom Gilbert

If not, it's not just like a big bag sitting there, but all the parts are there, ready to go.

00:02:29 Sandra Breum Andersen

Exactly.

00:02:30 Tom Gilbert

And so why do you, as an evolutionary biologist who is also into your microbes, like to play with these organoids?

00:02:38 Sandra Breum Andersen

I like to look at the interaction between the microbes and the host at different levels.

00:02:43 Sandra Breum Andersen

So we do mouse experiments as well, where we have the whole complex organism with a working immune system and lots of other microbes in the gut.

00:02:54 Sandra Breum Andersen

There we can do some types of experiments.

00:02:59 Sandra Breum Andersen

We also work with the human samples that our collaborators have collected for other purposes.

00:03:05 Sandra Breum Andersen

But growing these organoids allow us to go really on a much smaller scale to look at some of these interactions between host and microbes.

00:03:16 Sandra Breum Andersen

For me, the benefit is really that we can scale from the complex living humans with all of the noise that come from our environment and then really go zoom in to the cellular level.

00:03:28 Tom Gilbert

And so again, I think for many people who have not really experienced an organoid, maybe just the scale is worth asking.

00:03:34 Tom Gilbert

How big is one of these stomach organoids when it's ready to be played with?

00:03:37 Sandra Breum Andersen

Oh good. I actually don't remember.

00:03:40 Tom Gilbert

Not very big is the answer.

00:03:42 Sandra Breum Andersen

They're tiny.

00:03:43 Christina Lehmkuhl Noer

I think I remember you saying that you could grow hundreds organoids in a small well like and that is what, like essentially a lot.

00:03:45 Sandra Breum Andersen

Yes we can have hundreds in one of these wells, yeah. Exactly yes.

00:03:53 Tom Gilbert

So very, very, very small.

00:03:54 Sandra Breum Andersen

Small.

00:03:54 Tom Gilbert

So it's all work under the microscope.

00:03:55 Sandra Breum Andersen

Tiny.

00:03:56 Sandra Breum Andersen

And that's another thing that the organoidsallow us to do.

00:04:00 Sandra Breum Andersen

So when you when you have a mouse tissue with the microbes.

00:04:07 Sandra Breum Andersen

You can look at some things in the microscope, but it can be tricky to really zoom in, and that's what we can do more easily with these organoids. And the tissue cultures derived from the organoids. 

00:04:22 Christina Lehmkuhl Noer

Very cool. But so you say you are growing stomachs.

00:04:25 Christina Lehmkuhl Noer

Why is it stomach's not like other organs that you're interested in?

00:04:30 Sandra Breum Andersen

You can grow all sorts of organoids from the different tissues.

00:04:35 Sandra Breum Andersen

We are interested in stomachs because this inhospitable environment is actually the home of one specialized Helicobacter pylori that has been associated with humans.

00:04:49 Sandra Breum Andersen

Since before we were modern humans.

00:04:51 Christina Lehmkuhl Noer

When you say in hostile environment, is it because it's very acid acidic there in the stomach or yes?

00:04:56 Sandra Breum Andersen

Exactly. The pH is quite low in the human stomach about 1.5 and so not a lot of things can live there.

00:05:04 Sandra Breum Andersen

It's thought that's one of the reasons why we have acidic stomachs.

00:05:08 Sandra Breum Andersen

So that when we ingest something, if there's anything in there that can make us sick, then it gets killed off in the asset and it also helps start the breakdown of the food so that we can get nutrients from it.

00:05:23 Tom Gilbert

So this helicobacter pylori, which is your microbe of choice, it's a famous one.

00:05:27 Tom Gilbert

I believe there was even a Nobel Prize linked to it at some point and you mentioned it's been around humans for a long time, but I guess it was only really discovered in humans fairly recently, and maybe you can tell us more about it and why you find it so fascinating and why it's got that really important relevance for the yeah.

00:05:45 Sandra Breum Andersen

So, so in the 80s, early 80s, it was discovered that there was actually a microbe living in human stomachs and that it was associated with stomach ulcers.

00:05:55 Sandra Breum Andersen

Until then, stomach ulcers had always thought to be caused by stress in a poor diet.

00:06:02 Sandra Breum Andersen

And then two Australians found out that it was actually caused by Helicobacter pylori.

00:06:09 Sandra Breum Andersen

Then at that point, people thought, well, obviously then this is a bad thing. We should get rid of it.

00:06:16 Sandra Breum Andersen

And for some people, yes, that is probably a good idea. But in most people Helicobacter cause mild inflammation that we don't even know that we have Helicobacter.

00:06:28 Sandra Breum Andersen

And about 10% of infected individuals, they develop a stomach ulcer.

00:06:32 Sandra Breum Andersen

Also, and much rarer, but much more seriously is gastric cancer.

00:06:37 Sandra Breum Andersen

Of course, there are definitely some cases where it's a good idea to get rid of Helicobacter.

00:06:44 Sandra Breum Andersen

But not always.

00:06:45 Tom Gilbert

So there's this degree of complexity then that in some people makes you very, very sick.

00:06:50 Tom Gilbert

Where in other people, it doesn't have an effect. Why is that?

00:06:53 Tom Gilbert

It's not, as you said, just a stress related thing, a diet related thing.

00:06:56 Tom Gilbert

Think it's more than that?

00:06:58 Sandra Breum Andersen

So we know that.

00:07:01 Sandra Breum Andersen

Oh, we estimate that about 50% of the world's population are infected with Helicobacter at this time, and this used to be much higher.

00:07:10 Sandra Breum Andersen

So in a recent survey we did of Danish children, we found that about 15% are infected.

00:07:18 Sandra Breum Andersen

Whereas, for example in Colombia, where a lot of interesting studies have been done, it's about 80-90% of the population that are infected with helicobacter.

00:07:27 Sandra Breum Andersen

So our association with this microbe is changing and when we look at the causes of like who gets sick, when so many people have this bacteria, that's where the helicobacter comes in.

00:07:42 Sandra Breum Andersen

Because it turns out that at least part of what determines whether you get sick or not is the match between the microbe and the host.

00:07:53 Tom Gilbert

The match between the microbe and the host.

00:07:55 Tom Gilbert

So you have a certain genetic background in the host, and that means you're compatible with a certain kind of microbes that will give you symptoms or not symptoms.

00:08:03 Sandra Breum Andersen

So one of the neat things about helicobacter is when you do the phylogeny of the bacteria, you can track our movement out of Africa.

00:08:13 Sandra Breum Andersen

And so we have different strains of helicobacter that are most commonly found in certain air parts of the world.

00:08:19 Sandra Breum Andersen

And then, of course, there's been a lot of mixing in recent and past movement of humans, and so rarely you have a Helicobacter that's completely African.

00:08:31 Sandra Breum Andersen

A completely European, but they will often be a mix.

00:08:34 Sandra Breum Andersen

And so, of course, will the human genetic background to some degree.

00:08:39 Sandra Breum Andersen

And what was found in Colombia exactly, was that if you had a mismatch between the ancestry of Helicobacter and the host, then you are more likely to develop stomach cancer.

00:08:51 Christina Lehmkuhl Noer

So is that why your field is called evolutionary medicine?

00:08:54 Christina Lehmkuhl Noer

Because you can look at it back in time and like follow evolution?

00:08:58 Sandra Breum Andersen

Evolutionary medicine is a is a lot of things. It's how our evolutionary history contributes to our health and disease today.

00:09:10 Sandra Breum Andersen

And I am particularly interested in the microbial part.

00:09:13 Sandra Breum Andersen

So this is also for example related to our gut microbiomes, how they are changing over time because of our diet, because of the antibiotics we use.

00:09:25 Sandra Breum Andersen

And how that can give us a mismatch to the world that we are living in.

00:09:30 Christina Lehmkuhl Noer

You mentioned that it's only around 15% of Danish children. Who has it? So do we know why or how we lost all of this Helicobacter?

00:09:41 Sandra Breum Andersen

So the a part of it is probably less transmission, so transmission primarily happens from mother to child and it's thought to be the gastro oral route or the fecal oral route.

00:09:59 Sandra Breum Andersen

And so as we live in a more hygienic way, then there's probably less transmission from mother to child.

00:10:07 Sandra Breum Andersen

Adults probably also have lower loads of Helicobacter, maybe because they're using antibiotics.

00:10:14 Sandra Breum Andersen

And so there's less microbes to pass.

00:10:17 Sandra Breum Andersen

And so you can kind of see it as in for each generation there's less transmission.

00:10:23 Sandra Breum Andersen

And more eradication. And in in that way, the lower the prevalence drops.

00:10:29 Tom Gilbert

So I guess this raises the obvious question. Should we just get rid of it completely?

00:10:35 Sandra Breum Andersen

Yeah. So, so that was long the thought and still is for many in the clinical world that the only good Helicobacter is a is a dead Helicobacter.

00:10:44 Sandra Breum Andersen

And but what we see is that Helicobacter likely hasbeneficial effects, especially early in life.

00:10:51 Sandra Breum Andersen

So this could be one good reason to not get rid of Helicobacter.

00:10:56 Tom Gilbert

Beneficial in which way?

00:10:57 Christina Lehmkuhl Noer

Yeah. What benefits?

00:10:59 Sandra Breum Andersen

So if you are infected with Helicobacter, you are less likely to develop asthma and allergies later in life.

00:11:08 Sandra Breum Andersen

Life. And so this is thought to be a part of our old associates in the microbiome world. And so the microbes that we meet.

00:11:18 Sandra Breum Andersen

Early in life helped train our immune system so that we react in an appropriate way later in life to the challenges we meet.

00:11:28 Sandra Breum Andersen

And so this has been shown in humans through correlation that you're less likely to develop a range of diseases if you have Helicobacter.

00:11:37 Sandra Breum Andersen

And there's beautiful work done in mice showing that if you expose the mice early in life to Helicobacter, they are less prone to develop disease later in life. And so in this sense, the human and the animal studies support each other beautifully.

00:11:58 Christina Lehmkuhl Noer

Cool. I have another question.

00:12:00 Christina Lehmkuhl Noer

So you said that it can have like beneficial effects if you have it from very young because it can affect the immune system and protect against asthma and allergies.

00:12:12 Christina Lehmkuhl Noer

You know anything about how the bacteria because you said it's in the stomach, like how can it? How can it infect?

00:12:18 Sandra Breum Andersen

Yeah. So it it  while it's in the stomach, the  immune cells are constantly sampling who is there and is in that encounter.

00:12:30 Sandra Breum Andersen

That they tell the immune system to chill.

00:12:34 Sandra Breum Andersen

And take it easy and that these are good.

00:12:37 Sandra Breum Andersen

So we know that the timing is important here because early in life there's this window of opportunity.

00:12:44 Sandra Breum Andersen

Where you can.

00:12:45 Sandra Breum Andersen

Kind of assume that a lot of the things that you meet for the first time.

00:12:49 Sandra Breum Andersen

Something that you are supposed to be associated with and so it has to be in this period of time that you meet certain microbes and that affects them. How you meet other things later in life.

00:13:05 Christina Lehmkuhl Noer

So the so in the infants, their immune system is more.

00:13:09 Sandra Breum Andersen

Like a blank canvas basically.

00:13:10 Christina Lehmkuhl Noer

Yeah. So it's more open to accept. Yes, new, yes.

00:13:16 Sandra Breum Andersen

And that builds a tolerance to other microbes and other challenges later in life.

00:13:22 Tom Gilbert

So how does the Helicobacter actually lead to the damage?

00:13:27 Tom Gilbert

Caused in stomach ulcers or cancer or so.

00:13:29 Tom Gilbert

Is that the bacteria itself, or is that a body response to it and?

00:13:33 Tom Gilbert

Why does it not do that if it has the right host association?

00:13:37 Sandra Breum Andersen

Yeah, that the details of how the match matters, that is something that's being studied at the moment. So we don't actually know that well.

00:13:48 Sandra Breum Andersen

But it's in part in the response of the host cells to the bacteria.

00:13:53 Sandra Breum Andersen

So the bacteria have different ways of getting nutrients from the host cells and in that process.

00:14:01 Sandra Breum Andersen

They can damage the tissue and then again also the response from the host to these bacteria being present.

00:14:08 Sandra Breum Andersen

So we know that there's much more inflammation in when you're infected later in life because there's a much harsher response for the immune system, whereas early in life you have this tolerance to meaning.

00:14:20 Sandra Breum Andersen

New organisms.

00:14:21 Tom Gilbert

So it's very much partially driven by the host damaging itself in response to it.

00:14:25 Sandra Breum Andersen

Yes, so so yes.

00:14:26 Christina Lehmkuhl Noer

What are the perspectives of this research like?

00:14:29 Christina Lehmkuhl Noer

You think we end up infecting newborns with Helicobacter pylori to make sure that they get it early life or?

00:14:37 Sandra Breum Andersen

So no, I don't think so.

00:14:40 Sandra Breum Andersen

It's one trend we can see not.

00:14:43 Sandra Breum Andersen

But for example, there's a new probiotic with this bacteria called Acamencia, and there you can actually use dead cells and they still that the dead cell material of these bacteria enough to.

00:14:58 Sandra Breum Andersen

The immune response that has the beneficial if.

00:15:02 Sandra Breum Andersen

And so this is something that's also been looked at with Helicobacter.

00:15:08 Sandra Breum Andersen

To see and this has been shown, at least in my that the cell material is enough to elicit the beneficial effect.

00:15:16 Sandra Breum Andersen

I think this is going to be the way forward with many of these things.

00:15:21 Christina Lehmkuhl Noer

So you could infect the newborn children with dead bacteria just to train their immune system?

00:15:28 Christina Lehmkuhl Noer

So a little bit like a vaccine, I guess, but.

00:15:30 Sandra Breum Andersen

Yeah, so not infection, but a treatment, yeah.

00:15:32 Christina Lehmkuhl Noer

Yeah, interesting.

00:15:35 Tom Gilbert

So, given your expertise on Helicobacter pylori, what advice would you have to people who might have it already?

00:15:44 Sandra Breum Andersen

If you don't have any complications, then nothing I would say.

00:15:48 Tom Gilbert

That's good advice.

00:15:51 Sandra Breum Andersen

Of course, the curiosity of knowing, so I did screen myself and I'm not.

00:15:59 Christina Lehmkuhl Noer

I guess. Only if like only if you get sick, you'll actually know if you have it or not, right? And yeah.

00:16:06 Sandra Breum Andersen

I think if you are living in a region where there is where there is a high prevalence of gastric cancer, then of course it could be interesting to know before you develop severe disease, because then you could actually get rid of Helicobacter.

00:16:24 Sandra Breum Andersen

And hear something like knowing the match between your strain and yourself could be an indicator of whether you should treat something or not.

00:16:30 Christina Lehmkuhl Noer

Interesting.

00:16:31 Tom Gilbert

I have another fundamental question that may or may not be useful here. To get back to.

00:16:35 Tom Gilbert

Mentioned it can have no effect on you.

00:16:38 Tom Gilbert

It can cause stomach ulcers.

00:16:40 Tom Gilbert

Can cause gastric cancer.

00:16:42 Tom Gilbert

Is there kind of a logical progression from one to the other or can you get the cancer without the ulcers or the ulcers without the cancer?

00:16:49 Sandra Breum Andersen

Yes, there is kind of a. It's called Korea's cascade, so you have some steps along the way to develop cancer. And as I mentioned there at the earlier points, you can intervene and then when you're past a certain point then it's at least no longer beneficial to get rid of Helicobacter.

00:17:10 Tom Gilbert

So we've got this complicated situation where there's a.

00:17:14 Tom Gilbert

Seems like you might need it early in your life and it gives you.

00:17:17 Tom Gilbert

But on the other hand, if you get the wrong kind of it, it makes you sick.

00:17:20 Tom Gilbert

So I guess this is actually a growing observation with other bacteria out there.

00:17:25 Tom Gilbert

We can't view them as a black and white, good or bad thing, and I guess that really does allow you to change how you think about things.

00:17:30 Tom Gilbert

If we can get back to the organoids, I think it would be interesting to hear what you actually do with them on a day-to-day things. So you grow your organized, your little mini guts in a in your little tiny dishes.

00:17:42 Tom Gilbert

Then what happens next?

00:17:43 Sandra Breum Andersen

So one study that we've done is.

00:17:48 Sandra Breum Andersen

Expose mice to Helicobacter when they were young or later in life, and then compare them to mice that were not exposed.

00:17:57 Sandra Breum Andersen

So we take the tissue from the stomachs of these mice and grow them into organoids.

00:18:03 Sandra Breum Andersen

And these organoids never meet Helicobacter bacteria.

00:18:06 Sandra Breum Andersen

Yet we can see that the gene expression and the size of these organoids differ depending on whether the host was infected or not.

00:18:17 Sandra Breum Andersen

So we can see that the bacteria leave a mark on the host because they were there or not, and also depending on at what age the the mice were infected.

00:18:29 Sandra Breum Andersen

One experiment we also preparing to do is is look at the interaction between Helicobacter and so in again in this Hologenomic framework where we take into consideration the interaction between the host and the microbes and the environment. So for the host, this could be the genetic background, the age where it encounters the microbes.

00:18:56 Sandra Breum Andersen

And of course, we have different strains of the bacteria, with or without different products that they produce or mutations, and the environment could be the pH or the availability of of drugs and nutrients and these kind of.

00:19:12 Sandra Breum Andersen

Helicobacter and painkillers are the worst contributors to gastric disease, and so it's interesting to know what's the interaction between the two given that so many people have Helicobacter in the stomach and so we hope to do an organoid model of where we can vary the combinations of the host, so they would have tissue from different host that have genetic different genetic backgrounds. We would have different strains of Helicobacter producing different virulence factors or not, and then the possibility to add a painkillers and then see how these interact.

00:19:54 Christina Lehmkuhl Noer

So maybe it's not completely.

00:19:56 Christina Lehmkuhl Noer

That painkillers are also causing ulcers, but maybe it's like a a combination of the two, but also alone?

00:19:59 Sandra Breum Andersen

Oh, no, no, that's definitely right.

00:20:01 Sandra Breum Andersen

Yeah. Yeah, that's.

00:20:04 Christina Lehmkuhl Noer

OK, OK.

00:20:06 Tom Gilbert

So if you don't take antibiotics, can you naturally clear Helicobacter pylori? Or once you're infected, is it for life?

00:20:12 Sandra Breum Andersen

It looks like it's most often for life, yes, so I don't know this have a have a product called the Pylo Pass that can help you lower the burden of bacteria. They say without.

00:20:27 Sandra Breum Andersen

Interrupting the rest of the microbiome. So.

00:20:30 Christina Lehmkuhl Noer

The burden of Helicobacter pylori as well.

00:20:35 Christina Lehmkuhl Noer

It should be.

00:20:35 Sandra Breum Andersen

Specific to Helicobacter and in the trials, they see a relief of symptoms. So this could be a way to change your stomach microbiome, but without taking antibiotics.

00:20:50 Christina Lehmkuhl Noer

Hmm. So if you have like say, an ulcer or stomach problems and you think it's related to go back to.

00:20:59 Sandra Breum Andersen

So I think one problem has been that if you a lot of people when they have stomach problems they will get screened for Helicobacter and depending on which part of the world you live there.

00:21:12 Sandra Breum Andersen

A very good chance that you have Helicobacter in your stomach, but it might not be actually the cause of of disease. And then we enter this problem of using a lot of antibiotics that might not be needed and disturbing the rest of the microbiome.

00:21:27 Tom Gilbert

In addition to not being the cause, can it actually be beneficial for you when you're an adult to have it?

00:21:33 Sandra Breum Andersen

I think the benefits are most likely to be seen early in life during this priming of the immune system. What we also know is that.

00:21:44 Sandra Breum Andersen

Once you are on the path to towards developing.

00:21:48 Sandra Breum Andersen

There is a point of no return where even if you eradicate Helicobacter, it's too late, so that you've already seen some of these mutations in the tissue.

00:21:59 Tom Gilbert

It's a really fascinating topic that things can be good and also can be bad.

00:22:02 Tom Gilbert

I guess I'm curious to. I come back to do we have other major examples that affect humans or even non humans, where you have a similar system where depending on who you are.

00:22:14 Tom Gilbert

Or what situation is a microbe might be good for you or for sure over the edge?

00:22:20 Sandra Breum Andersen

I think for a lot of the human microbiome we would, we thought by now we would have identified the good and the bad guys and I think a lot of it comes down to it's a balance of not having too much of one thing.

00:22:35 Sandra Breum Andersen

And again, then also when we look at a much finer scale, not just at the species level, but what's the Max match actually between the host and the micro?

00:22:46 Tom Gilbert

So it's complicated.

00:22:47 Christina Lehmkuhl Noer

Yes, I know some.

00:22:49 Christina Lehmkuhl Noer

They are starting to say that they can, like, look at your microbiome and tell you like what probiotics should you take or like, like what diet?

00:23:00 Christina Lehmkuhl Noer

Or that and what do you think about that?

00:23:03 Christina Lehmkuhl Noer

Do you have anything?

00:23:04 Sandra Breum Andersen

Yeah, I mean, you can't really do that yet.

00:23:07 Sandra Breum Andersen

I know there are some studies in Israel where they're really looking at a lot of parameters, so they are tracking.

00:23:17 Sandra Breum Andersen

Individuals glucose levels after a meal or everything they eat, sampling their microbiome, and there they say that they can use the composition of the microbiome is one factor in predicting, for example, what would be a beneficial diet or not. But to the general person sending in a bit of their poop.

00:23:36 Sandra Breum Andersen

Nope, not unless you have a. Of course, a very clear pathogen of some sort, but other. Not.

00:23:43 Sandra Breum Andersen

Unfortunately, it's too complicated and I think it's good to remember that when you find these patterns in big studies, it's usually thousands, or at least hundreds of individuals where you see.

00:23:54 Sandra Breum Andersen

A pattern in one or the other direction, but that might not mean so much for the individuals.

00:23:59 Christina Lehmkuhl Noer

So speaking of stomach samples, I know that you have this really cool project with the Copenhagen Zoo abou developing new ways of sampling the stomachs.

00:24:10 Sandra Breum Andersen

Yes, we have a new project that I'm very excited about.

00:24:14 Sandra Breum Andersen

It's also in collaboration with with any poisonous group at the DTU where they've developed a device to samples stomach contents.

00:24:23 Sandra Breum Andersen

It's a smart pill that.

00:24:26 Sandra Breum Andersen

And then it takes a sample in the stomach and then you can collect it in the feces.

00:24:32 Sandra Breum Andersen

So this is something that we're going to try out in this.

00:24:34 Tom Gilbert

It's like a mini excavating submarine. You swallow that.

00:24:38 Christina Lehmkuhl Noer

So what it opens up in the stomach and then it closes again when it's taken.

00:24:40 Sandra Breum Andersen

Yes, exactly.

00:24:42 Christina Lehmkuhl Noer

Exactly. Yeah. Nice.

00:24:44 Christina Lehmkuhl Noer

Can you actually then take these pills and then grow them? In the lab.

00:24:50 Sandra Breum Andersen

We're not growing them, so we're just looking at who's there basically at this point, yeah.

00:24:55 Christina Lehmkuhl Noer

Sequencing everything and looking at it genetic, OK.

00:24:57 Sandra Breum Andersen

Exactly. Exactly.

00:25:01 Christina Lehmkuhl Noer

Interesting. So that might give you a much more diverse view of who is actually inside the stomach.

00:25:07 Sandra Breum Andersen

Yes. And what's the pH of stomachs and all of these questions?

00:25:12 Christina Lehmkuhl Noer

What animals do you sample?

00:25:15 Sandra Breum Andersen

Well, tigers is one that we're very excited to try out.

00:25:20 Sandra Breum Andersen

There's obviously a lot of challenges with sampling the live animals, so it has to be an animal that has a fairly large esophagus.

00:25:29 Sandra Breum Andersen

It cannot be chewing too much on.

00:25:33 Sandra Breum Andersen

So gulping is good.

00:25:36 Sandra Breum Andersen

There's also the challenge of actually finding this device afterwards in the fecal material.

00:25:42 Sandra Breum Andersen

And so the vet had a brilliant idea.

00:25:47 Sandra Breum Andersen

Of adding glitter to the to the meal that goes in with the device so that we know which poop to look for.

00:25:55 Christina Lehmkuhl Noer

That will help the zoo keepers, I'm sure.

00:25:59 Christina Lehmkuhl Noer

So they don't have to go through all of them to find the device.

00:26:02 Tom Gilbert

So I've known you a long time.

00:26:04 Tom Gilbert

I knew when you were a proper evolutionary biologist back in your master's and PhD days, and I'm curious, how did you then transition into this interest in Helicobacter pylori and human health angle?

00:26:15 Sandra Breum Andersen

Yeah, so I started working with at the Centre for Social Evolution where it's about how organism interact with each other when they cooperate. When they start cheating and their relatedness is a big part of it.

00:26:30 Sandra Breum Andersen

You are helping other organisms that you are related with because then you pass on your own genes.

00:26:37 Sandra Breum Andersen

And from there on, I wanted to move into something more related to human health.

00:26:41 Sandra Breum Andersen

And so I worked with social evolution in bacteria causing lung infections.

00:26:48 Sandra Breum Andersen

And so there's been this general thought that when we see pathogens infecting humans over time.

00:26:57 Sandra Breum Andersen

That must be an adaptation to the host that they're in and, for example, antibiotic treatment and so on. And we wanted to test the idea whether some of these changes in the bacteria over long infection times were actually due to the bacteria interacting with each other.

00:27:15 Sandra Breum Andersen

And so we looked at bacteria that started out cooperating.

00:27:19 Sandra Breum Andersen

And what we saw often was that the bacteria stopped cooperating.

00:27:23 Sandra Breum Andersen

And what we could show was that actually they stopped cooperating because they start cheating.

00:27:29 Sandra Breum Andersen

And so this is a strategy that can win out in the beginning.

00:27:34 Sandra Breum Andersen

Don't pay the price of cooperating.

00:27:36 Sandra Breum Andersen

Still get the advantage.

00:27:37 Sandra Breum Andersen

And so we saw that these interactions between bacteria actually matter for evolution in a host.

00:27:44 Sandra Breum Andersen

That was somewhat easy to do in lungs because these toy these were long pathogens and they were the dominant Organism in the lung.

00:27:53 Sandra Breum Andersen

So I wanted another bacteria that was dominant in its environment and that made me drawn to Helicobacter and another thing that I really liked was that it has these both beneficial and harmful effects.

00:28:09 Sandra Breum Andersen

This is something, as an evolutionary biologist and someone working with symbiosis, it's always fun to have.

00:28:16 Sandra Breum Andersen

Scale of interactions and see what's the tipping point that makes it harmful or beneficial.

00:28:22 Christina Lehmkuhl Noer

Thank you so much Sandra for taking your time here today with us and making sure that we are aware that the bacteria are not just good or bad, but it's important to look into all the implications around them.