Microbiology (GUT BIOME) with Elaine Hsiao

Oh kay, it's that friend who never carries a purse, which must feel so liberating. But also she always asks you to keep her lipstick in your purse and you're like, well, okay, I mean sure. Ali Ward back with another episode of Ologies. Boy, Howdy hot, damn you all this one is. It's super exciting. This is like introducing someone to their future spouse. Like you're about to not know what hit you. Okay, First,

The charts every week.

I read you a very piping hot tongue burner of a review fresh off the press.

We speak.

Painted Novus says, this podcast is the Cloaca of science facts. It's got a little bit of everything going on. I can't stop talking about trees and squid arms and the long long life span of sharks. I'm putting a solitary bee house in my yard and fighting to overcome my fear of snakes and legless lizards. Thank you, Painted Novus. I think a snake would love to have you as a friend. To be honest, Okay, microbiology the workings of

Okay.

Now, I had email this ologist repeatedly, creepily, over and over for the better part of six months. I thought this would never happen. Honestly, I had pretty much given up hope until we finally found a time we could boastit down in her office on the UCLA campus where she runs her own microbiology lab. Also in her office on a couch a pillow in the shape of the poop emoji, but with hearts for eyes. True story the Ologies Instagram has proof seek it out.

Okay, So this.

Ologist has authored so many papers about the inner drama and triumphs of the critters that live in our guts and ostensibly make us us and I am in very unsubtle, very obvious awe of her work. I was freaking out. I was also very sweaty and frazzled because even though I got to campus half an hour early, the parking was a hellscape, and I walked into her lab fifteen minutes late. Did you do the math on that, because that means it took me forty five minutes to park.

She wasn't even mad at me. So please pat.

Your belly and let the trillions of tiny, invisible friends who control your mind get ready to listen to gut biome expert and microbiologist doctor Elaine Shao. Once again, I'm sorry that I'm so sweating.

No, I like to arrive moist to my interviews. Just Dewey, And what is your title?

It's assistant professor in Integrative biology and Physiology.

Oh, a lot of ologies.

I know.

I was going to say, do you think that you are molecular biologist, a microbiologist, physiologist?

What would you call yourself?

I am a crisis ologist, I in to many things. Yeah, so our work touches on microbiology, but we also use molecular biology approaches, and it also touches on neurobiology.

We'll go with microbiology. We're just we're going with microbiology because you're like one of those D and D dice with all those different facets. You're like a twenty sided oh DND dice pretty much. Oh man, that was too nerdy, too soon.

When did you decide that biology was for you?

Yeah?

So I did choose a biology related major. So I had to make the decision in high school. To be honest, at the time, it wasn't that informed. I wasn't one of those kids that just love science forever know, nobody.

In my family does science.

I was really into other things like performing arts and music.

But I just thought that I had to choose.

Something practical, and I'd just taken biology in high school and I thought it was neat, So that's my little choice at that moment. Thankfully, it turned out well, so I stuck with it.

And now you have your own lab, which means that you're the boss, which is pretty dope. What was it like, Do they have a ribbon cutting ceremony? What happens when you get your own lab?

There was no ribbon cutting.

Basically, you get faced with an empty space and then you have your pot of money and then you just go and there's no instructions on how to set it up. So different labs will have different styles and you know, different structures, so it's really.

Up to you.

I mean, that's so boss.

It's fun. It's really fun.

Yeah.

Did you think when you started out in biology that you would go this far with it? Did you think that you'd be kind of heading operations like this?

No?

No, Actually, I first decided to enter grad school because I thought that I really enjoyed teaching and that's all I wanted to do.

And in the.

First half of grad school I seriously considered dropping out, like.

Not really doing well.

Yeah, but afterward, you know, things started rolling and kind of got the hang of doing research and just really got sucked in and I really love it.

Now.

That's interesting though, that you were that there was a kind of a hump to get over and then you're like, okay, oh wow, I'm really good at this. Like you see people who are so successful in what they do and you think, oh, it must have just been kind of a straight path, you know.

Yeah, not at all for me.

But what really kept me in it is the science is a lot of fun. You know, there's a lot of room for creativity. You get to decide what you want to study, and you get to decide on what the important questions are, and then you get to decide on how you're going to try to answer those questions. So I find that it's really fun.

Yeah.

Elaine studied microbology during undergrad and at that time, the program's focus was really on the so called bad bugs that cause infectious disease.

But then she became.

Fascinated by the somewhat neglected study of for drama's sake, we'll just say the good guys, the helpful bugs.

I was just watching this new field develop where more of the focus now is on good bugs rather than bad guys. The bad ones turn out to be super small portion of all the bacteria that are that are out there. So yeah, that's how I became interested. It's just watching the field develop and wanting to, you know, help explore.

Yeah, and so we focus on these bad bugs because they can take us down. But meanwhile, how many things do we have living on and in us? Because there's always that number you hear that's like ten to one, because one of for every cell of yours there's maybe ten microorganisms.

Is that total bullshit?

I mean, no pun intended.

You know, the actual numbers are a little bit fuzzy. It gets down the nitty gritty. It depends on what you count as a cell. So there are some cells that don't have a nucleus, so they don't have like the DNA that you're thinking of. If you had to give someone, like a dinner party estimate of how outnumbered you are, what would you say, Like, roughly, I would stick to the ten to one. I would actually I

Your gut, What about your nose and your eyes and your hair and your mouth and stuff. They're everywhere, and they're everywhere so quick aside, why do we call these bacteria bugs?

Anyway?

So the etymology of the word bug is ancient Welsh for ghost or goblin, which in this case kind of makes sense. You figure invisible, scary things that can exert mysterious forces on us. I mean, yeah, it tracks. So Elaine is essentially a ghost hunter who's just out looking for caspers. And so what makes a good bacteria versus a bad bacteria?

Yeah, that's a good question.

I mean, a very superficial level normal is that they don't actually cause disease.

And now people.

Are finding that the bugs that are in and on us that some of them play really important roles. Like there's some bugs that help us digest things that we wouldn't otherwise be able to digest, Like there's no way, like the complicated fibers in your granola bar, there's no way ourselves could actually digest that ourselves.

We rely on bugs to help us do it.

Yeah, So if there are certain foods you can't eat, do you think you just need better bugs?

That's a good question.

I think, you know, some people are actually studying that, and yeah, I think that's an active area of research.

Interesting.

Okay, going back to going back to your research a little bit. Was there anything at the intersection of biology and psychology that really intrigued you? How are you studying all these different ways that our stomachs and our guts, our intestines affect our brain.

That's nuts, that's so cool. What was it that intrigue you about that?

Yeah, the same thing that you're mentioning is what really sucked me in. I started grad school not really intending to study bacteria at all. We were studying in my lab. My mentor's name was Paul Patterson at Caltech, and he kind of pioneered these animal models for studying autism and also animal models for studying schizophrenia. And it was really just noticing that at the time, if I changed the microbiome somehow, that these mice started behaving differently.

Oh my gosh, It's like, oh this is really weird.

I can't stop. I'm getting sucked into this.

I need to know why.

I mean, so, we're puppets to a bunch of strangers, friendly strangers that are living like in our colons.

Essentially, you could.

Put it that way, but the lines are getting blurred. It's like, do you count them as strangers or do you also count them as self? You know, there's no animals that don't there's no animals that exist without microbes, so some people like prefer to count them as part of yourself.

I mean they're definitely close collaborators. Yeah, I'd have to say, well, it's a team effort over here, definitely.

Yeah.

I think that's the idea now, is that there's this maybe what people like to say, like, oh, coevolution. Then you know, we grew together and they do some things and we do some things, and it's this symbiosis.

You know, it's so it's so bizarre, and it also makes you feel never lonely.

Have one hundred jillion friends at least a big party.

Yeah, you're that, You're a party bus is what I like to think of it. As can you explain to me.

A little bit how the things that are living in your guts how they affect your brain?

Yeah, that's a great question. At this point, the field is really excited just by you know, acknowledging that they do affect behaviors so most of it this work comes from animal studies, Like if you study mice or or flies or fish, if you get rid of the microbiome, then they start behaving differently, or if you change the microbiome, then they'll behave another way. And now labs are just trying to figure out how that happens. What are the

So they might be putting out some kind of chemical, some kind of signal and your brain's like, oh, got it, ten four, I'll do that.

Or they might just be.

Like pooping out things and our brain is receiving them being like, oh, I think I'm going to go in this direction just from having them pass like a blood brain barrier.

Is that it that works? Yeah, exactly.

So that's a really good and that's a really good reference that some molecules that bacteria make can cross over. It can get absorbed into the intestine, can get into the blood stream, and some of them can enter the brain across this blood brain barrier.

I don't even know what a blood brain barrier is, but I just said it because it sounded like I knew it.

I was, Oh, really, it sounded like that. It was perfect. It was perfect.

It's basically that not everything you know that's in the bloodstream enters the brain, and so there's this barrier like sandwiches of many cells that are there that kind of you know, are the gatekeepers of what can enter real quick.

So I looked into this, and so the blood brain barrier is a semi permeable situation that happily lets in water, some gases glucose, which is delicious sugary think fuel. And in some cases, like with neurological disease or trauma or inflammation, this blood brain barrier can become more lax, kind of like a bouncer who gets distracted by their phone and starts admitting douchebags like toxoplasmosis, lime causing bacteria, syphilis, and

Oof. Okay, so when you're looking at human beings.

Are you like we are all maybe a little bit off of our rockers, just gently because our diets are maybe so different than they would be in the wild. Is there a really big correlation like the fact that we're eating honey crisps for breakfast and like a Venti frap for lunch, Like, is that really screwing us over a lot?

So that's also a huge area of study in microbiome work,

Is there any truth that our serotonin is made largely in our intestines?

Yeah? Absolutely.

So that work was from Michael Gershon and he first published this finding that about ninety percent of the body's serotonin is made from gut cells.

Yes, that's so many numbers, that's so much.

It's made in our guts. It's just simmering in our in these big hoses full of poop down there.

Yeah.

Well, the gut is so cool. It's not just a container. It's really important that they hold poop, but they're really cool. There's actually a lot of neurons that are in there, maybe like five times more than in the spinal cord.

Wow.

So yeah, there's a lot of neurons that you know are there. It's one of the few organs that if you take it, if you sever it from the brain, it can work by itself.

Yeah, oh my god.

Okay, So, if ninety percent of your serotonin is made in your gut, what cells are pumping it out or is it the bacteria that are pumping it out?

So there are these endocrine cells that are basically cells that are in the gut lining and their role is to make lots of serotonin and some hormones, so they do things like control your appetite, when you get full, when you feel nauseous, things like that. And yeah, what we found a couple years ago, oh, is that bacteria are really important for communicating with these cells to control how much serotonin is being made and released.

Oh my god, my colon is blowing my mind right now. How do you ever look at like the way that we treat depression and anxiety and are you ever like on the sidelines being.

Like you're doing it wrong.

We wonder how much the gut plays a role even in side effects. So it's known that antidepressants have a lot of like GI related side effects. It's important to study, you know, how the systems interact. That being said, there are dedicated neurons in the brain that make the remaining you know, ten percent of serotonin of the body, and those are really important for depression too.

But gosh, that sounds like when you think someone's the boss and then you find out that like it's the assistant does all the work, you know what I mean? Yeah, yeah, if you could just go ahead and make sure you.

Do that from now on, that would be.

Great because you'd think the brain, thanks for the serotonin. You're doing you're doing your job, but downstairs is just a serotonin factory. Yeah, how does serotonin even make us happy?

Yeah, okay, that's a really good question. So in the brain, it's serotonin is a really important neurotransmitter and it's only made from certain neurons, so very select few of neurons make it. And so it's thought that these the serotonin will activate these circuits that are really important for things like reward and happiness. And yeah, that's how people think

Ultimately, and our animals are people who are depressed, do they have less serotonin than people who maybe aren't depressed.

I think that's one thing that could happen. I feel like there's probably many different you know, pathways that contribute to depression. But yeah, decreases in serotonin are associated.

Man, I feel like you're going to look back. We're all going to look back and be like, oh my gosh, it was so obvious, like what caused certain things? You know, when you look back at medical practices of your and you're like, that's horrible.

How did we do that?

Yeah, that might be that might apply with the vehicle translates right now.

Maybe like remember the days you.

Couldn't go to like a jiffy loop type of a situation where you just pop in. I'm just gonna pop in for a quick feak. Trans You're like, Okay, when you describe your job to someone who's never met you, how do you talk about it?

Like, what do you say that you do?

Yeah, that's a good question.

It depends on I would probably give a boring answer about you know how. I'm a professor, I run a research lab and I teach. But to lab members, I often tell them that I'm the hype person of their work. They make really cool findings. I communicate the findings, I pitch the findings to try to get funding more funding for their work and so I'm kind of the hype person for what they discover.

Your job is just so fascinating, Like I mean, you know that I have been like kind of mildly stalking you on email for a long time.

I'm like, Hi, can we record?

How can we record?

I'm just like so fascinated by this field. But how do you kind of describe the importance of what you do to people?

That is a really good question because I'm still not good at it.

Usually, you know, when you're.

On an airplane and you have like a couple minutes to talk, I'll give an explanation that I'll just shut down the car station. What okay, But let me think of a cooler way, maybe taking you know, recommendations. Maybe one way I should explain it is that we study how gut bugs control brains.

So allow me to be the hype man for the hype man, but holly, actual shit. Elaine studies have involved some truly wonderful and very important things like the microbiomes effect on neurotransmitters, how it relates to autism, and even how the microbiome can affect seizure occurrence in epilepsy.

It's big stuff.

The most recent stuff we are studying is really whether we could use microbes to replace dietary effects on the nervous system. So we chose this diet. You may know the ketogenic diet. It's kind of a fad diet right now, but it's been used for almost one hundred years to treat epilepsy.

So side note.

This ketogenic diet is high fat and very very low carb like max thirty grams a day or lower, depending on how you do it and your frame of reference. Maybe Joe Rogan proselytizing like a shredded pastor, or maybe you have a coworker who just like drops a dollup of coconut oil in her coffee and only eats the toppings off of a pizza. But research shows that keto can reduce seizure occurrences by half in half of the patients, and a third of patients report up to a ninety

In kids that don't respond, to normal medications that are out there as a last resort treatment, they'll often get enrolled in the hospital and put through this really severe diet. And so we wondered if we could study whether the microbiome changes and whether the microbiome is important for how

So instead of doing the diet, would you maybe be able to increase that proportion of microbes to affect seizures.

That's the idea the calveat is we've done that all in mouse first, you know, to start. Who knows it will work in people, But that's the pie in the sky, is that we'll either be able to have say a very specific probiotic or a companion treatment to help the diet work better, or even you know, the extreme version of this, if we can have this type of treatment replace the diet entirely so that people can you know, cheat or be on normal diets but still get the same.

Kind of effect.

And then what about microbes and gut flora and autism.

Yeah, that was actually my grad work.

So now we're going to kind of my first works in the microbiome field. The reason I got into the microbiome is came really intrigued by this finding that some cases of autism are correlated with lots of gi abnormalities.

Oh so some kids with.

Autism have severe gi abnormalities, not all.

Of them, but some of them.

And you know, for the fundamental biology, I always like to you know, keep it, you know, temper my enthusiasm where you know, a lot of things that are found in animals don't translate well to humans. So there's a big gap there, but I think inspires.

You know, more work to be done.

So if we do a good job on studying mechanisms and animals, then we can justify studying kind of similar pathways in humans and maybe doing some you know, safety trials to see whether the microbiome related treatments we tested in animals are also safe and effective in humans.

And what was the mechanism in terms of the autism or the epilepsy that told the brain to work a little bit differently. Yeah, so we don't have all the answers. But what is really cool is that a lot of gut bacteria have this unique chemistry that they can, you know, make biochemicals that our body doesn't normally have. And so we became really interested in what for the diet story, what are the microbes doing with these components from the

Story, we also were looking at, you know, in this context, what do microbes make, what do their molecules do to neurons, things like that.

So they may have been making certain chemicals that made neurons fire differently.

Absolutely, Yeah, So in the epilepsy work, we think that they're making they were metabolizing molecules that ultimately restricted GABA, which is inhibitory ner transmitter. So GABA is this molecule in the brain that neurons use usually to silence activity. So we were seeing that these microbes were controlling brain levels of this molecule that is like telling neurons to quiet down, and we think that's what's helping with seizures.

So the dietary change upped the GABA in the brain and reduced seizures, so potentially very life changing all because someone had the sense to think, I wonder if these trillions of tiny animals living in my intestines are sending messages to my brain loaf when you have people who are looking at your work and they're like, boy, howdi hot dam that's a big deal. And then we go to the store and we're like whole foods in the probiotic aisle, being like, which one of these will make

Oh? Man, those are the hardest questions to answer, because on the one hand, I believe in the promise of probiotics and what bacteria can do. But on the other hand, the stuff that's on the shelves and the supermarket, they.

Weren't rigorously tested to.

Treat disease or to be anything more than nutritional supplements I think.

And also some of those probiotics have bugs that.

Are not native to the body, So there are things that came from dairy or fermented foods which are really different from bugs that are normally in the body.

So yeah, those are so hard.

I can't even advise on which ones work or not.

I did take.

One before, just to see if I felt any differently, and I didn't.

But that doesn't mean that it doesn't work.

There are some people that respond really well to them, especially some people that experienced GI problems or have intestinal disease. Probiotics could help.

So the bad news is that despite the thirty two billion dollars we citizens of Earth spend yearly on probiotics, they may not be effective. I read one report in the Anals the Annals the Annals of Internal Medicine that certain shelved brands of probiotics can be harmful to folks who already have shaky floor to begin with. And there was a recent New York Times article that noted that the studies are almost all low quality, small in size,

It's party a clock for those little motherfuckers.

I feel like this is just a new field that's just cracked open, and we're all peering in, being like, what's gonna happen. This is amazing because we just never we never even looked at any kind of psychological or mental health issues. We never really looked at those as like a holistic like a full body situation.

Yeah, it seemed like.

We it's so cool to think that we're all here when this field was born, you know, like it was only maybe ten years ago that people even were able to name the bacteria that we're in the body, and the majority of them no one knows.

Anything about what they do.

And so now now is the time it was just born and people got to get in that people have to get in on this to study it.

I feel like you're kind of like a cosmologist of butts. Like there's so many stars in the universe, and then there's so many things we don't know happening every day. I mean not of butts specifically, but in general. But it's like this unknown that's so important to us. But when it comes to anxiety and DEPRESSI because we've talked about autism and epilepsy. When it comes to anxiety and depression, how does gut flora affect those flora?

Really interested in that a lot of anxiety and depression is also comorbid with GI problems, and so some people are really curious about whether we could use microbes to correct GI problems and influence you know, these disorders right now in animals. Again, I always like to like distinguish in animals. We can clearly see that behaviors that are related to anxiety and depression seem to be changed when we change the microbiome.

Okay, I'm sorry, I'm trying to contain myself.

But again I can't. It's not always a one to one from a mouse is not not a human. Yeah, so what kind of things are these mice doing? Are they just like scrolling on social media too long and like talking about their ex boyfriends too much? Sure?

Yeah, I mean everyone is at this party, and probably my ex is like with a new girlfriend who probably has a way longer tail than me. Mine is so short and stumpy, no one will ever meet with me. I'll never have a litter of forty babies, some of which I might eat.

Okay for real, So, though, what do anxious mice really do?

There's a lot of really cool behavior tasks that you could put them through.

They don't. They're pretty benign.

Is just you know, for one, common anxiety task is just to put them in a box. Usually they'll just you know, kind of be scared and be around the edges of the box and after a while go and venture into the center. So that's kind of what people measure as an anxiety related behavior. And when you treat them with SSRIs or anxiety drugs, you can see that they change the duration of time that they spend along the edge versus center.

Yeah, gosh, they're actual wallflowers. Yeah.

Who knew that was a thing. Yeah, let's get down to the nitty gritty of your work. So you have a stuffed poop emoji sitting next to me.

How much of what you do is cultured matter from our bodies or other people's bodies?

Where are you getting them? How do you keep track of them?

Yeah?

So we do usually start with poop itself, So we'll often take either even like human poop, or we usually start with animal models and we'll sequence well, you know, for example, in the diet study, we take mice, we put them on the ketogenic diet, and then we sequence off of their poop to see how the micro.

I am changed.

And once we get some interesting hits from that sequencing, then we might get like very specific species and culture them in the lab. And those you can usually buy from there's from a culture collection, like there are companies like nationwide or country specific culture collections.

Real, Yeah, like a catalog of bugs you could just flip through. Yes, that you're like, I'll take a lactobasilicus or whatever exactly exactly.

And you just buy them and we can grow them in the lab.

And so when it comes to sequencing, what happens when you're sequencing things but you they're unknown species.

Yeah, so sometimes that happens. And what you can do is keep tabs on those what those sequences are, and then you just kind of consider them as unknown or like new species when you analyze them. Okay, but that's a big problem too, is that not everything.

Has been identified.

How many different species do we have in our guts?

People say that across humans that over a thousand different species have been identified from the microbiomes.

Yeah, do you get tripped out by microbiology and all? Like are you when you touch a keypad at CVS or something, are you like what am I touching? Or are you like you know what?

The more the merrier when you study microbiology, you realize that there are a lot of bugs that are just normal, and that it won't kill you to be exposed, that maybe some of them are really important for educating your immune system. So exposing yourself is not that bad. Of course, you don't want to take it to an extreme. There are things that I would not do, like don't lick the door?

Yees?

What do you think of the hygiene hypothesis? Just a side note, So this is a theory proposed by British epidemiologist David Strachan in nineteen eighty nine.

Ps.

He might pronoun set stracken and I'm sorry, but essentially this theory says that the rates of autoimmune conditions and allergies have gone up in Western cultures because of sanitation and antibiotics and smaller family size means exposure to less diverse microflora. Also, Western cultures have something called low oro fecal burden and I google that with one eye closed for safety, and yeah, it means what you think, it means less pooh in our mouth. So the hygiene hypothesis

I think it's really interesting.

Yeah, this idea that you should encourage your kids to go play in the dirts so that exposure to microbes helps educate your immune system and protect from chronic diseases, I think, yeah, I think that's really interesting. I haven't seen anything that is outright refuted that idea, only things that have kind of supported it.

So we're maybe a little too clean for our own good.

When you look at big population white studies, definitely you could see that we're really good at treating infectious diseases, so historically that rates of infectious disease have gone down, but rates of chronic diseases like you know, metabolic disease A diabetes and obesity and multiple sclerosis, things like that have gone up. There's a different problem now that's not infection. So people wonder whether it's just this we're too clean for our own good.

Wow, Like it feels like whack a mole with diseases, you get one and another pert. Yeah, what is the correlation between multiple sclerosis and gut biome? I did want to ask that because my mom has MS super quick. If you're not sure what MS is, I'm going to do a PSA right now because my mom has it

Now.

If you're not affected by MS, this info is important too, because chances are that you or someone you know is affected by an autoimmune disease and has an immune system that somehow got jolted up and is cleaning attacking things that you don't want it to. So if you know someone with an autoimmune disease like rheumatoid arthritis or hair loss, or psoriasis, or lupus, type one diabetes celiac, this inflammation and autoimmune disease is of interest.

First people were studying how the microbiome interacts with the immune system because there's a situation where, you know, if you've got one hundred trillion bacteria in the gut, how do we keep them in check? And the way that we do that it's that you know, about eighty percent of your body's immune cells are right there, and it's this boundary where there's like microbes talking to immune cells

Is that used in any kind of therapy at this point or are we still so far off?

I think people are developing that, so I know people are taking that to human studies and so I'm not sure how far along it is right now in what phase of trials, but it is being developed.

So if we very very highly suspect that the microbiome is involved, what kinds of illnesses are being treated through restoring a healthier one, like through a doctor. Not as much as you'd hope yet.

The only thing right now that can be treated with microbiome is C. Difficile infection, so an intestinal infection. That's the only thing that currently is being treated with these fecal transplants.

We wanted to get there.

That was on my list.

Yeah, I mean I had so many patrons that asked about it, and it was like, gonna be on my list because I feel like.

There's just this like like a golden cure that's a poop transplant, but it's not legal yet, and it seems like it's a bit frowned upon, But yeah, can you run me through what is a vegal transplant?

Yeah, so it is.

It is legal for se diff infection. So in this infection, basically there are some people they'll get this basically opportunistic pathogen. So this bug that's normally in a lot of us, but can turn bad in certain situations and then cause intestinal disease. And usually the first line of treatment is antibiotics.

How is that actually done?

Yes, so it's much better now, So, oh God, back with it before before, I think Before, I think that you would actually have to find a donor, usually someone in your household, and you'd go in and the donor would poop and.

Then you would get enema of what they gave and that was the treatment.

Nailed it.

Now there are more controlled, you know, materials to transplant with, so you can buy from a company that really rigorously screens what was in there and what's being transplanted, and they make sure that it's safe. And so the doctor can either buy the liquid material or they could have capsule versions.

Oh so I started looking into this and I think, I think this is a prescription formula with a very romantic name called VSL number three, which has nothing to do with PSL's pumpkin spice lattes or going number three if you know what I mean. Though, it does help with it and in one newspaper of India it was reported that this could help the condition of Lucy's which is a word I will never forget. No matter how

So it's legally.

Called medical probiotic food, which is perhaps a more palatable administration than say some other methods.

So you could either take a series of like several capsules in a row, or what's what works.

Better is if you get that enema.

Basically, yeah, do they have to make sure that you're pretty much clear of the bad ones?

So do you have to take a ton of antibiotics first?

Yeah? I think so you take antibiotics first to clear out and then you immediately transfer it.

What do you think about people who are doing it just pinterest DIY style.

I've seen that. I mean, it's really dangerous. Who knows what you know?

If I wouldn't, You wouldn't know what's in it until you sequence it and really test it. And now that people are studying the microbiome so deeply and finding like neurological things that are related, or metabolic or chronic diseases that are related, you don't want to be in this situation where you cured your ce diff but then you predisposed yourself for other diseases in the long run.

You know.

Yeah, so I would recommend not doing it at home, but I can see that, you know, people are eager to try since since currently you can only use that treatment for this one intestinal disease.

Yeah, I wonder if that's going to change in the future. I'll be like, Okay, we let we let ibs in. Okay, we let arthritis in. Or you know, just different different ailments will get the pass for it, you know.

Yeah, I wonder too. Or you know, alternatively, people are trying to, you know, parse out the transplant material into just the select bugs that are important, and maybe you'll just have cleaner capsule.

Versions for each of these diseases.

Or yeah, is that slurry of fecal transplant that doctors obtain is that from a donor base.

It's from donors, Yeah, heavily screened professional poopers. Are they good question? I'm not sure, But I think you can make a good living off of it.

I bet you can, because I mean, you'd have to be even better than a sperm donor. I feel like, like, because you'd have to make sure that you had the best work ever, right, you gotta look up their salary. I bet it's pretty good, maybe more than the doctors who knows. Okay, citizens of planet Earth, you're welcome. I

I dropped my wallet in a Starbucks toilet. It was flushed, but I was.

Like, I there was a moment where I was like, I don't know what to do do I just cut and run? So I grabbed it out of the toilet with a bunch of tissue and then I washed my hands forever, and then I like sprayed bleach on it and then I bleached everything in there.

But like, am I gonna die?

No, that's exactly what I would have done. I probably would.

I would have fished it out and just you know, washed it was so the bleach will do it for sure.

Okay, that's okay.

I used to decan't decontaminate things in the lab.

Okay I did.

I sprayed everything with like a bleach solution afterward, in that wallet is now in the garbage.

But I was like, what do you do?

And then I thought, well, you know what, maybe this will be good for me.

Yeah no, no.

Not good for me. Oh my god, what a whrror?

And so is there anything that's kind of on your list that you want to study next, like any particular angle that you really want to go for.

Yeah, we have a lot of things going on in the lab. I mean, at the end of it, what we really want to study is how is the microbiome doing so many things behavior? What are the molecules, what is the pathway? You know, what's the cascade of events that's happening to allow them to do things like that? And we study these mechanisms and lots of context. So

So right now you have tiny critters just gabbing over your influx of morning coffee like doe, old men gossiping in a.

Park over a chest set.

Now, who funds this microbiome research.

Do pharmaceuticals fear.

The day when we can get good pooh for free to fix of our problems. So funding, Elaine says, comes from some federal sources and the National Institute of Health. Even the Department and Events want to study the mental and physical health of deployed personnel. The EPA is even getting in on the action figuring out how environmental toxins can make our microbiomes take a hit. So there are

Yeah, so antibiotics are not specific, they're broad spectrums, so they'll kill you know, the bad bugs, but they'll also kill off your microbiome too.

Whoa.

And so after you're on antibiotics, then you basically need to repopulate. Your microbes will grow back and repopulate your body basically.

So this is like the cops come and shutting down your party because there are a few obnoxious guests, like even your trusted pals tossed out the door. Cops are like, I don't care if she was your maid of honor and is cleaning up empty cups. That guy over there is wrapping along the sublime and getting the dog high.

Everyone is out, and so people are really interested in how do you control this? How do you get them to repopulate correctly, back to healthy state rather than into some alternate like poor microbiome state.

Yeah, how do you do that?

Yeah that's right, Yeah, nobody really considers that. One question is whether, you know, maybe after a course of antibiotics, should we be considering taking you know, a probiotic to replenish or transplants to replenish the microbiome correctly. People are considering the same idea for sea sections. For example, if you have sea section babies, they end up not being expose the same types of microbes, And does that mean we should inoculate them immediately so they do grow a normal microbiome?

Yeah?

What happens?

Because if you're squeezing out of the v I imagine you probably get a little something from the back door on you and you're like thanks mom. She's like I couldn't help it, but you enjoy it. But if you see section you skip all that. So do they swab babies with a little bit of poo or what happens?

Yeah? Right now.

I don't think it's normal practice in the US, but in some other countries I think it is normal to kind of, you know, swath the baby in mom's stuff.

Stuff stuff, miscellaneous items, things with possessive personal effects.

That's the creations.

Yeah, just like a little dabble doo.

Yeah, and yeah, how do you interact with kind of pop or spa science when you see articles on like Goop or Instagram products that are like.

This too will restore your whole microflora?

Like, are you like that's a little true? Are you like, oh my god, how dare you?

I mean, what grad school and science trains you to do is be skeptical of anything.

We have everything, So that's my default.

If you could give one tip to people about how to build a good microbiome, would it be just like, don't wash your vegetables as much if they're organic? Like, how do we do it without running through whole foods and spending a bunch of money? I think what is safe to say, hopefully this is not just more of what we already knew is that you could eat a diversity of different fibers to feed all of the different

Is wow. I never thought about that.

I read that Martha Stewart eats the same bagel, the same bagel sandwich every morning.

She's got to dive. If I heard gut bacteria.

You sequencing steady, I know they're just like it's the bacteria that like a bagel with a slice of onion or.

Whatever it is.

I swear to gut that I read this somewhere, and I just want you to know. I spent over an hour while on semi vacation in Hawaii, sitting on a porch with slow as fuck Wi Fi trying to fact check this, and now I think I just hallucinated it because I can't find it anywhere. But I did learn that every morning Inagarten eats the same coffee and an oatmeal, and Mariah Carey's diet consists of just two items Norwegian salmon,

We feel better if we're eating a lot of fruits and vegetables.

Yeah, diversity of fibers mainly is what the carbs basically is what they eat on complex carbs. Do you ever notice that if you eat terrible food that you feel kind of grouchy for a couple days.

I do.

It's so good in the moment and then after where it is just remorse.

Can we do a rapid fire around? Yeah, all right, these are questions from listeners. They were so pumped, they're so excited. Okay, but before we take questions from you, our beloved listeners, we're going to take a quick break for sponsors of the show.

Sponsors. Why sponsors? You know what they do?

They help us give money to different charities every week. So if you want to know where Ologies gives our money, you can go to Alleyward dot com and look for the tab Ologies gives back. There's like one hundred and fifty different charities that we've given to already, with more every single week. So you need a place to go donate a little bit of money, but you're not sure where to go. Those are all picked biologists who work in those fields, and this ad break allows us to

Riddia Aguinnis Tyler, Beth Frosto, Lisa Tang, Mark Larson, Nickenna Hopwood, Serene Karaga, Jamie Katananch Kennedy and Tony Thompson.

Is kombucha really worth all the hype? What's the deal with kombucha? Can kombucha actually be helpful. So many kombucha questions.

Oh man, okay, these are hard.

I mean, in general, I think that I've only seen the positive things, if not neutral things about fermented foods. So kombucha included fermented drink. So I think it's definitely doesn't seem harmful and if anything, it could only help.

Yeah, okay, it's yeast, it's it's a fungus an a bacteria, right.

Yeah, that being said, and a lot of people make their own kombucha at home, so you've got to be careful that you keep the culture clean because sometimes there are these rare cases of growing. You know what the scobie, Yes, what it stands for?

Okay, So a scoby stands for symbiotic culture of bacteria and yeast. And it looks like a beige, flabby, slimy disc that feels in texture what I imagine preserved dolphin skin might feel like. And after finding a feathery brown thing in my store bot kombucha, I thought I'd do a science And now I have grown it and it is sloshing around in a large jar in one of my kitchen cabinets. It's just growing larger and larger and probably more sentient by the hour.

Now if you.

Smell them, I would say Scoby has kind of an acrid musk, which I imagine is similar to the groin of an ox. But they brew some great, fizzy, yummy stuff. It kind of tastes like a mix between a snapple and a PBR.

And I mean that in.

A good way, like kind of gross. But I know Scoby, I trust me.

I have grown them, and they are like a big, slimy pancake in a jar.

It's more frightening than the things we grown. But yeah, there are certain cases, I think rare cases where they got contaminated with maybe pathogen, and it was like, really made people sick.

Be careful with your Scoby.

Okay, good to know, so probably couldn't help unless you got unless you get a bad apple. Yeah, And so many people asked al Martinez, A Forrest, Craig Curry.

Also Henry Strong, Christopher and Brewer, Ryan Moore, Athena Alas Ferri, Caitlin Donald and Sarah Weas.

Everyone was like, do stowbought probiotics? Do anything?

Yeah?

I think that it's another case for certain people they seem to really help, especially people that have GI problems or intestinal diseases that it seems like they can help. Actually, there's one case that of a medical grade probiotic for intestinal diseases that truly seems to help.

Then your doctor prescribes.

It the aforementioned spy name sounding yes.

Okay.

Another Patreon question, PA Foxhall asked, what is the weirdest thing you've learned about how the gut microbiome influences us so far?

Oh, weirdest thing. Let me think.

None of it seems weird now because we study it so deeply. I mean, I think one thing, it's not super weird, but we're really interested in this idea that that gut bacteria can control these neurons that connect Basically, they touch your gut and they extend directly in the brain. And so that's weird idea that there's like this long telephone where gut bacteria can send these molecules and control messages that are being.

Sent up to the brain.

So that's one thing that I think is really cool, maybe kind of weird.

Cool is that the vagus nerve, the vegas nerve.

Yes, I mean, so from what I understand, this is how I envision it, which is probably wrong. There's like a nerve, like a corny thread fiber that just hangs out from your brain to your stomach, and it's just like a remember those pneumonic tubes where they would send like bank tellers would send checks through, And it's just like that, but with feelings. And I know that that's not right. But what exactly is that vegas?

No, I mean that's pretty close. It's a bundle of neurons.

On one end it touches is your brain stem, and the other end it touches a bunch of different organs. And so there are the fibers that extend to the intestine too, and they are bidirectional, so you can send messages up. Some of them relay messages up into the brain, and other neurons relay in the other direction from brain back to the gut. And so yeah, that's how they work.

Oh my god, that's so weird. What happens if they sever that?

Yeah, a lot of things. It's so.

Animals wand up having behavioral problems. This has actually been done I think historically in people too. Is vagueotomies.

Yeah, I don't know.

What the original indication was, but their outcomes from it.

Yeah, So vagotomies. All right, I look this up.

In animals with damaged vegus nerves can gain weight even with super restricted diets because the signaling that turns off energy storage and turns on burned energy gets whack. So yes, and in humans this can lead to increased insulin and increased fat storage. So vegas, nerve important.

Vegas, baby vegas.

I'm guessing they don't do those anymore.

I don't think so.

I mean, that's another thing where you know, they used to be like someone acting up, give them a lobotomy. Yeah, you know, I think we'll look back on the way that we treat mental illness as like.

Oh man, we really did that wrong.

Yeah.

So anonymous Bob wants to know which.

By the way, Anonymous, you said your name was Bob, So anonymous mob okay. But difference between pro and prebiotics.

Yeah, So probiotics is where you have the actual cultured bacteria the bacteria, and then prebiotics is related to what I was mentioning before, where different bacteria have different food preferences. So prebiotics often have very specific types of fibers basically that will feed a certain type of bacteria. So prebiotics is giving food that will enrich particular bacterium, and then probiotics is where you give the bacterium itself.

It's so cute to think of our little bacteria as like little fish that we have to feed, you know what I mean.

That kind of to sprinkle use some prebiotics. I hope you like it.

Yeah, And we do that with our diet all the time. And I guess it's so interesting too that we're like, oh, it's good to eat a lot of fiber, and part of that might be just to feed all of our little dudes.

Yeah, and ladies. And I mean they're asexual, you know. Let's see.

Todd McLaren wants to know do various microbes have a form of brain.

Oh, that's an interesting question.

So they don't have a brain, of course, they don't have any organs through the single cells, but they can still do really cool things. They have behaviors. They don't have an official brain.

Though, but they can still do stuff, yeah, and have preferences. Evidently they're like I love a rootabaga. Tom Meyer says, to what extent is a septic system and extension of our digestive system. A septic repair person told me some things. This sort of blew my mind real.

I was like, oh my god, Oh my gosh, I want to know, because I have no clue how to answer this.

Look this up and again you're welcome. Yes, true stuff. So, in a twenty fifteen paper entitled Sewage reflects the microbiomes of Human populations, researchers reported that quote the distribution patterns reflected human population variation and predicted whether samples represented lean or obese populations. With get this and eighty one to eighty nine percent accuracy, scientists can analyze sewers and figure out whether or not the population is lean or obese.

Oh okay, that's also a really interesting one. I mean, in general, in the lab, we'll use certain alcohols to basically decontaminate things.

So we think that, you know, particular alcohols will probably kill bacteria. But I'm not sure.

I feel like these studies must be underway now is what people are looking at as how like sequencing studies or something in response to drinking. Yeah, I don't know the outcome, so right.

I imagine if you're drinking a lot of Ever Clear on Friday night, but maybe your gut bacteria is.

Like, oh no, yeah, are you doing this to me?

That's interesting?

Ariel asks, have you investigated these gut brain interactions in species with different types of digestive systems? I'm thinking specifically ruminants who have such a rich gut microbiome and if that plays a role similar to.

What you've seen in humans and mice.

Oh yeah.

So as a field, my lab doesn't study ruminants. We mainly study animals and or mice, and sometimes we'll get human microbiomes to study, but they're definitely labs that do study ruminant microbiomes and it's really cool. As a grad student, I did one rotation through a termite lab studying termite microbiomes and basically what allows termites to digest wood is the microbes that are that they have. So yeah, I think studying microbiomes across species is really cool and will be important.

That is interesting because ruminance guy got a whole other. They have so much work to do. We got so much cellulose. I gotta brete that stuff down. Kathy Arnell says, okay, gross one for me? What is the culprit of the intensely grotesque smell that emanates from my hubby's time in the back room? And she says, I'm not talking about the average smelly pooh, but the kind that drives you from the room. No discernible pattern happens five six times a month. I believe that his biome is whack.

Oh wow. I have no clue.

I mean, normally this would be like methane gas or something. But if it's unusual, there are other Actually there's there are microbiomes that are being studied that make this molecule that underlies the like fishy fouls, fishy odor. So maybe there's are microbes that could be related there.

And in general, people.

Are really interested in how microbes can make molecules with different odors and like where the microbes make chemicals that are basically like olfactory cues.

Yes, oh wow, so they might be telling other microbes by stinking a certain way inside us. They might be telling other microbes to do something certain things.

Yeah, that they actually yeah, kind of are determinants of different sense. And so there are some labs that are also studying microbiomes on the skin and maybe that they can make olfactory chemicals that influence how likely you get bitten by a mosquito.

Yeah, Oh that's nuts. Let's see.

Tyler Q wants to know. Is it true that your gut influence is what you want to eat more than your brain does.

I'm not.

I think that's a really cool question, but nobody has really shown in definitively. I'm really interested in that too, since if microbes have food preferences, I'm really interested in micro food preferences influence my food preferences. Yes, I haven't seen anyone shown show that yet.

Okay, so quick aside. I watched this documentary on Vimeo. It's a short documentary called gut Hack, and it's about noted biohacker Josiah Zeyner's quote grueling and grotesque DIY fecal trans plant. And apart from the fact that he appeared to do a lot of the dirty work in his kitchen, I was struck by how after he finds that the donation from a healthy friend was successful. He's looking at the gene sequencing of his new microbiome and he starts breaking down.

That is pretty insane.

The experiment actually worked.

I don't know. I haven't like crying.

This is crazy, which was very moving. It's one of those things where you're just so moved and impressed by how science works or just how.

Yeah.

Side note, he also developed the same sweet tooth as his buddy, So your sweet tooth is really really deep in your bowls Metaphorically, I have heard that if you eat, you start eating a healthier diet, you start to crave that more.

Yeah, so, I don't know.

Eleenia Zach, Eliana Zach, and Kayla Jane both had questions kind of about Crohn's disease, alterative colitis and and ibs, like, if someone has debilitating symptoms like that, you know, are there any suggestions you have for good gut health that might also help?

Well?

Yeah, so I think with the alternative colitis that that might be a situation where where you could talk to your gastroentrologist about this, like.

Medical grade probiotic.

I'm not sure if it as actually indicated for UC or if it's some other variant of IBD, But all of those disorders that you just listed off, I think maybe kind of next in line for microbiome based treatments that get to humans after cedif of sill infection. I think maybe the most likely candidates would be these types of disorders.

So we're kind of going to start using them on the guts and then work our way up to using them for the brain.

Probably maybe maybe I wonder if it'll ever get up to the brain. I think if we can really do a good job on the science side, then yeah, that it would maybe that would be a possibility in the future.

Well, you're like doing that, It's amazing. I mean that's I'm like, huh, I'm sorry, that was a sound of me fan girling. Also, if we live in close proximity with others, do.

You think that our gut biomes are kind of contagious?

Oh, that's a good one.

So it is known that people that live together have more similar microbiomes to each other, and that your pet has a more similar microbiome to you than to some stranger whoa So I think there is some degree of sharing and transfer.

Yeah, So I wonder if your partner has a certain like let's say depression, anxiety, or serotonin deficit. If you can kind of influence each other's microbiome and then you're like, oh, we both got to get ours on track.

Oh, that would be crazy. Yeah, I'm not sure.

But I mean if we if we end up finding if science tells us in the future that the microbiome is the root of, you know, certain diseases, and I think this type of transfer or sharing would become a big issue.

Yeah.

And what's the part in this but the shittiest thing about your job, Like what's the hardest, the most annoying, the most tedious. Just what is the one thing that you hate about your job?

Yeah?

Oh man, there's just a lot of I mean, I was not trained to be a good manager, but there's a lot to manage. There's a lot of little nitty gritty things to manage all at once, you know, like safety related things, coordinating purchasing, and so I personally do not enjoy getting stuck in emails and administrative duties.

But it's not I can't complain.

You know.

That's the price you pay for having an awesome job.

Yeah, for having your own lab Yeah, being the captain of the ship. What do you love the most about your job?

Oh?

I love the discovery part so fun. I mean everything, there's always new things going on, So I love working with the students and seeing data that they're producing and all the cool discoveries going on. I also really love conceiving, like new projects, things that we should work on in the near future.

Do you have like a list that you keep, like in a moleskin notepad of like things I'd like to discover?

Almost I have a really plain Excel document that's called projects or experiments or something, and a list of everything that I would love to work on sometime.

Yeah. Oh, what's on there?

All sorts of things like what you mentioned this food preference idea, whether microb's influence our food choices. Oh, there's just so many things. Usually when people come to the lab, I like to, you know, let them study what they enjoy. But if they can't think of something, I'll pull up this document and say, hey, what about that one.

It's like ten foot scroll. Yeah, it produces out of a cloak.

I have some ideas, and it seems like you could do this for decades and decades and still have so many questions to answer.

It never ends. It never ends.

Actually, the more that you discover, there's just like more questions and it's just exponential, like yeah, curiosity.

Basically, well, you're doing such a great job. I'm a literal fan of your work. Thank you so much for doing this. So gather your guts and ask smart people stupid questions because chances are the questions are not crappy. So to learn more about Doctor Show's work, check out show dot Science, h s I AO dot Science, or you can find her on Twitter at pipett hero p I p e t h e r O pipet hero I will link both of those things in the show notes.

Please calm down, Okay, bryebye.

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