Intro and Outro: Hello and welcome to the Microbiome Medics Podcast.

I'm Dr.

Siobhan McCormack.

Intro and Outro: And I'm Dr.

Sheena Fraser, and we're your co-hosts.

We are both GPs and lifestyle Intro and Outro: medics with a shared passion for microbiome science.

Intro and Outro: We'll be translating the evidence and packaging it into actionable, Intro and Outro: bite-sized chunks so that you could harness the power of the microbiome to improve Intro and Outro: your own health and that of your patients.

Siobhan McCormack: Hello and welcome.

I'm Dr.

Siobhan McCormack and today's microbiome medics topic, Siobhan McCormack: which is the role of the gut microbiome in surgery, has kind of blown my mind Siobhan McCormack: mainly due to the work of today's guest.

Siobhan McCormack: So microbiome science draws on many disciplines, microbiology, Siobhan McCormack: gastroenterology, genomics, ecology, evolutionary medicine, metabolomics, Siobhan McCormack: machine learning, the list goes on and on, but I have to say I've never really Siobhan McCormack: considered surgery to be a central part of this team.

Siobhan McCormack: That changes today because of this professor from the University of Chicago.

Siobhan McCormack: He's a colorectal surgeon, a gut microbiome research pioneer, Siobhan McCormack: the world-renowned expert in post-operative infections, and a radical thinker Siobhan McCormack: whose research findings on the role of gut bacteria in post-operative infections Siobhan McCormack: I think have practical applications far beyond the Operating Theatre.

Siobhan McCormack: Professor John Alverde, welcome.

John Alverdy: Thank you so much, Siobhan, Dr.

McCormick, for the invitation to join.

John Alverdy: And it is an honor and a pleasure to be here.

John Alverdy: And we will just freely associate.

Siobhan McCormack: Absolutely.

Well, I wonder if I can start by asking you to introduce yourself to the listeners.

John Alverdy: Sure.

So I am a general surgeon, a general gastrointestinal surgery.

John Alverdy: My clinical practice was focused on the foregut, the esophagus, John Alverdy: the stomach, the gallbladder, the pancreatic obiliary tree.

John Alverdy: And I became interested in, John Alverdy: with colorectal surgery because it has a high failure of healing when two pieces John Alverdy: of bowel are brought together.

John Alverdy: And it's particularly problematic when a leak occurs in the colon anastomosis, John Alverdy: which has the highest density of bacteria.

And, you know, it's a life-threatening problem.

John Alverdy: People don't like to talk about it.

People don't like to admit that they've John Alverdy: had leaks, but no surgeon is immune.

John Alverdy: You know, there's no surgeon that I know of in the best hospitals in the United John Alverdy: States and in the United Kingdom that has not suffered this complication.

John Alverdy: And when it happens, it's devastating to both the patient and the surgeon because John Alverdy: it's rare, but it is life altering, because the surgeon, we call them the second victim, John Alverdy: feels that something he or she did had something to do with this thing not healing, John Alverdy: because so many times it does heal.

John Alverdy: And it's been dogmatically explained away by surgeons as a technical error, John Alverdy: which we think we've dispelled that.

John Alverdy: It's not due to a technical error.

How is it that you got 90% of them correct John Alverdy: and only 10% of them leaked?

How did that happen?

John Alverdy: Well, you know, it's biology.

It's complex.

John Alverdy: It has to do with the tension and ischemia and this and that.

John Alverdy: And they explain it away without any hard evidence.

Siobhan McCormack: Most people, including your non-surgical colleagues, have a pretty two-dimensional Siobhan McCormack: view of colorectal surgeons.

Siobhan McCormack: You know, you go to work, you open someone up, you wield your scalpel, Siobhan McCormack: you do some magic stuff, you close up, you drive home, you come in the next Siobhan McCormack: day and do the same again.

Siobhan McCormack: What does being a surgeon mean to you?

John Alverdy: Being a surgeon means that you have to see the patient, understand their pathology.

John Alverdy: Prepare the patient and the family for what you're about to do.

John Alverdy: Then you have to get there early in the morning, John Alverdy: talk to the family, talk to the patient, make sure everything is properly checked John Alverdy: off, that they've stopped any anticoagulation, that their medications have been stopped, John Alverdy: that they were nothing to eat or drink after midnight, John Alverdy: that their bowel, for example, if you're doing colorectal surgery, John Alverdy: that their bowel has been properly prepared for the surgery.

John Alverdy: And then you do your surgery, which can take four or five hours, John Alverdy: but then you worry after that because you know you're depending on the patient's John Alverdy: nature, their biology to heal what you've done.

John Alverdy: And there's some uncertainty there, Yet you have to be at the ready to meet John Alverdy: any challenge that you're faced with, whether it be an infection, John Alverdy: bleeding, any kind of postoperative problem.

John Alverdy: And, you know, I think non-surgeons think of this, or maybe the lay public, as a manual task.

John Alverdy: It's just a person performing a manual task when there's so many judgments that John Alverdy: take place, so much of an intellectual discipline that takes place before you.

John Alverdy: Do the actual surgery.

So this is an old aphorism in surgery.

They say, you know, John Alverdy: great surgeons know when to operate.

John Alverdy: Even better surgeons know how to operate.

But the best surgeons know when not to operate.

Siobhan McCormack: Wow.

Yeah.

John Alverdy: And so that aphorism is sort of like, you know, how do you make a judgment that you should not operate?

John Alverdy: So I don't know if you've ever read the book, Cutting for Stone, John Alverdy: you know, he wrote in there, I violated, when he operated on a patient that John Alverdy: died on the table, he said, I violated the first commandment of surgery, John Alverdy: never operate on the day of the patient's death.

John Alverdy: I thought that was brilliant.

Siobhan McCormack: Yeah, I mean, you do, I do, I've listened to a few of your talks, Siobhan McCormack: you do seem to draw from literature and from, you know, the past, Siobhan McCormack: And there was one quote, which I think you recommended your students read, a paper by Crummel, Siobhan McCormack: which was 2006 or something.

Siobhan McCormack: Surgery is not an operation, but an intellectual discipline.

John Alverdy: That's correct.

Siobhan McCormack: And I've just never thought of it like that.

Siobhan McCormack: If we can, we don't often get to go to the theatre.

Siobhan McCormack: I haven't done it for years.

You know, I qualified in 1989.

And I remember the Siobhan McCormack: theatre is quite a frightening place.

I always seem to get the scrubbing up Siobhan McCormack: wrong and it seemed very kind of intriguing and mysterious.

Siobhan McCormack: So can we invite the listeners into your operating room at the University of Chicago?

Siobhan McCormack: Can you show us around?

What are you wearing?

What does the room look like?

Siobhan McCormack: And can you introduce us to some of the team?

John Alverdy: Sure.

So, you know, the first thing you do is you're wearing surgical attire John Alverdy: so that you're dressed properly.

John Alverdy: And you first have to go to a bin and pick up ostensibly sterile clothes that you put on.

Siobhan McCormack: Are they still greens?

John Alverdy: They're greens, they're greens, we call them greens, yeah.

And then you, John Alverdy: walk into the operating room and make sure that the patient's positioned properly John Alverdy: for the operation that you're going to do.

John Alverdy: Then you introduce yourself to the nurse.

And there's two nurses, John Alverdy: the circulating nurse and the nurse that's going to be the scrub tech who's John Alverdy: going to hand off the instruments.

John Alverdy: There's the anesthesiologist and his or her team of people to put the patient John Alverdy: to sleep and make sure that they're secure and that they will give blood when needed, et cetera.

John Alverdy: And they have a very important job.

And so you had this whole team.

John Alverdy: And then you have, at least at the university, you have, you know, John Alverdy: students, residents, and fellows who are there to train and learn from you.

John Alverdy: And, you know, I always find it fascinating that at least in British English, you call it theater.

John Alverdy: We call it an operating room because it actually is a theater.

John Alverdy: There is a performance going on.

And there is an audience watching this performance.

John Alverdy: And, you know, the performance is supposed to, you know, have the right crescendo, John Alverdy: decrescendo, and it's all supposed to be beautiful and timely and, John Alverdy: you know, orchestrated, choreographed properly.

John Alverdy: And so I think theater is a better word than room.

It's not a room.

It is a theater.

Siobhan McCormack: Yeah.

I remember being quite frightened just scrubbing up.

And I don't know if Siobhan McCormack: you can just go through from memory for me Siobhan McCormack: it was you know I was kind of terrified of one was looking at Siobhan McCormack: me to make sure I was doing it properly when you went as a medical student to Siobhan McCormack: watch an operation and it seemed quite a Siobhan McCormack: laborious process that could go on for five or ten minutes you Siobhan McCormack: were you know had to be really careful you have these special trough-like basins Siobhan McCormack: and you moved the taps with your elbows so that you didn't touch anything with Siobhan McCormack: your hands and you you got a brush and you were brushing we had to brush for Siobhan McCormack: like five minutes we had these slightly frightening nurses looking over us And Siobhan McCormack: if so much as moved or touched the wall slightly, Siobhan McCormack: they were then like, no, stop, start again.

Siobhan McCormack: You have to take everything off and, you know, start again.

Is it still like that?

John Alverdy: Yes.

And, you know...

John Alverdy: One of the myths or dogmas that we're trying to dispel is that all infections John Alverdy: from surgery come from some type of external contamination event.

John Alverdy: So you bumped into something, something fell out of your nose or your hair or whatever it is.

John Alverdy: And so to maintain sterility in the operating room is very important.

John Alverdy: You scrub for a long time, you have the right clothes on, you know, John Alverdy: you cover your head.

And people keep trying to study this.

John Alverdy: And thankfully, and a lot of this work was done in the United Kingdom where, John Alverdy: you know, we've gone from the 1920s to today to go from where we had a 30% infection John Alverdy: rate after surgery down to somewhere about 5% or 10%.

It's low.

John Alverdy: And that's because of the sterility and the antibiotics and all the other precautions that we take.

Siobhan McCormack: So that has worked to an extent, but then we're going to talk about where it's Siobhan McCormack: not working or where actually there are problems.

Siobhan McCormack: So I know that you consider the patient the most important person in the room.

Siobhan McCormack: So I don't know if you or I can conjure up a typical case that I think you might Siobhan McCormack: see or whether you wanted to sort of paint a picture of a patient or?

John Alverdy: Sure.

So a typical patient would be, you know, a patient who, John Alverdy: would undergo, let's say, a colon removal, you know, removing their colon because John Alverdy: they either have inflammation or a cancer.

John Alverdy: And you would make a, I'm going to stay in the field of maximally invasive surgery, John Alverdy: not minimally invasive.

John Alverdy: So, you'd make a big incision down the middle of their abdomen, John Alverdy: and you'd open them and sterilely prep everything.

John Alverdy: So, you'd make the incision after you've prepped and draped them and, John Alverdy: you know, made sure that you maintained sterility, gloved and all that stuff.

John Alverdy: And then you'd make an incision and you put in a wound protector to protect the edges of the wound.

John Alverdy: And then you would do the operation, which is to remove part of their colon John Alverdy: and then take the piece that you've removed, the two ends, and connect them together.

Siobhan McCormack: And that's what you call anastomosis.

John Alverdy: That's what we call anastomosis, right?

And, you know, back to your other point, John Alverdy: I just want to throw in one anecdote, which I found very interesting.

John Alverdy: I went to medical school in Mexico and watched babies being delivered by a midwife.

John Alverdy: All came out normal.

Then I came to the United States where I spent a year at John Alverdy: Loyola University's medical school.

John Alverdy: I remember walking into this operating room and bumping, to your point, John Alverdy: bumping into the IV pole, the intravenous pole that was holding the IV fluids.

John Alverdy: And I bumped to it, and the professor yelled at me.

He said, John Alverdy: who's this medical student?

What the hell is he doing in here?

John Alverdy: Go back and scrub again, to your point about the nurses watching over you.

John Alverdy: And I'm back there scrubbing, and I re-draped and everything.

John Alverdy: And I thought to myself, and it was a delivery.

John Alverdy: I don't know why I was in this particular case.

But I said to myself, John Alverdy: does this person know that like 90% of the babies delivered on this earth are not delivered this way?

John Alverdy: It's not in a sterile operating room.

John Alverdy: It's like out in the open in their home by a midwife who's, you know, John Alverdy: being as clean as they can.

John Alverdy: But, you know, and all the babies look normal to me that I was watching being delivered to Mexico.

John Alverdy: And I had come to the United States and, you know, we're in this operating theater John Alverdy: and, you know, everything's sterile and don't touch anything.

John Alverdy: Thing in your life, wait a minute, John Alverdy: this is kind of at odds with what goes on in the rest of the world.

Siobhan McCormack: And I suppose it's all based on the germ theory of disease trumps everything still.

Siobhan McCormack: And this idea that all microbes, particularly bacteria, are all highly pathogenic Siobhan McCormack: and dangerous and must be avoided at all costs.

Siobhan McCormack: And I suppose this whole, you know, microbiome science has completely revolutionized Siobhan McCormack: the way we think about microbes, that a small percentage, Siobhan McCormack: I don't know if you know the percentage I'm guessing I don't Siobhan McCormack: know I read somewhere six to ten percent of all the Siobhan McCormack: bacteria on earth are potentially pathogenic to Siobhan McCormack: man but most of them are either disinterested or free Siobhan McCormack: riders but then we've got this group that are incredibly beneficial Siobhan McCormack: and so it's this idea of this kind Siobhan McCormack: of you know ecosystem within where we're always Siobhan McCormack: focusing on the few bad guys or and Siobhan McCormack: we'll talk about that because there's no such thing and we'll talk about Siobhan McCormack: sort of virulence and virulence factors later on but um Siobhan McCormack: yeah so it is kind of really interesting uh Siobhan McCormack: but it's also interesting how difficult it Siobhan McCormack: is to change shift perspectives uh Siobhan McCormack: even in the face of you know very good evidence but um so this this you know Siobhan McCormack: let's say this 43 year old uh gentleman that we're operating on maybe the father Siobhan McCormack: of two kids um he's you know incredibly anxious he's been diagnosed with colorectal Siobhan McCormack: cancer at a young age, which maybe we'll discuss again later.

Siobhan McCormack: Maybe he's had some chemotherapy, radiotherapy.

Siobhan McCormack: Maybe he's not in good health generally, if he's anything like the normal population.

Siobhan McCormack: A poor diet, lots of ultra-processed food.

He may have other pre-diabetes.

Siobhan McCormack: He may be on a couple of medications.

Siobhan McCormack: His family are waiting outside anxiously.

It's all depending on you.

Siobhan McCormack: How does that feel for the surgeon?

John Alverdy: Yeah.

So, you know, we work in teams.

John Alverdy: You know, most of the time that patient will be, John Alverdy: at least over the course of my life, I've seen that responsibility was originally John Alverdy: all on the surgeon to know what medications to stop, John Alverdy: which ones to start to prepare the patient beforehand.

John Alverdy: And now all of our patients go to pre-op anesthesia clinic, where an anesthesiologist John Alverdy: spends time with the patient, goes through their medications, John Alverdy: and then tells them which ones to stop, which ones to take, John Alverdy: and reinforces what the surgeon's preferences are for that particular operation.

John Alverdy: But to your point, no patient goes to the operating theater that has no disease.

John Alverdy: These are sick people.

And I think that's what you're trying to paint the picture.

John Alverdy: This patient's coming to the operating room because they have a disease.

John Alverdy: That disease might be cancer.

John Alverdy: And not all, but most cancer patients have underlying comorbidities, John Alverdy: to your point, diabetes, hypertension, obesity, etc.

John Alverdy: And, you know, we're all trying to be as healthy as we can be, John Alverdy: but some people aren't as healthy as a doctor thinks they should be.

John Alverdy: And therefore, they're now about to undergo an operation.

John Alverdy: And, you know, many times we'll see a patient and we will send them to their John Alverdy: general medical doctor for what we call medical clearance.

John Alverdy: And I'm about to do a four-hour operation.

Is this the best shape you can get John Alverdy: them in for their diabetes?

John Alverdy: Is this the best shape you can get them in for their hypertension?

John Alverdy: Is this the best shape you can get them in for their weight problem?

John Alverdy: And can, you know, how urgent is the surgery has to be balanced against how John Alverdy: much time, you know, you have.

John Alverdy: And these days, I think, you know, we like to think of, for elective surgery, time is your friend.

John Alverdy: You know, most people that are old, they have an orthopedic problem.

John Alverdy: It's not urgent.

John Alverdy: They've had the pain for months, if not years, and they're about to undergo John Alverdy: a big operation.

And, you know, time is your friend.

John Alverdy: You could wait a week or two or a month, and we'll get into that later, John Alverdy: which we call dietary prehabilitation.

John Alverdy: You know, what is the impact of dietary prehabilitation on outcome from surgery?

John Alverdy: That's going to be a big issue over the next 10, 20 years is can you get somebody John Alverdy: in better shape and improve outcome?

Because, John Alverdy: Um, as I mentioned before, we've gone from 30% infection rate down to 10%, which is good.

John Alverdy: Thank, thank you to all the antibiotics and the sterility and attention to detail.

John Alverdy: But how do we move the needle from 10% down to zero?

John Alverdy: You're like more of the same.

Just do more of what you're doing, John Alverdy: more sterility, more antibiotics.

John Alverdy: And the answer is no, because antibiotics are indiscriminate in their killing.

John Alverdy: They kill the good guys and the bad guys.

John Alverdy: And you're like, well, sterility, more sterility.

No, you're killing both the John Alverdy: good bacteria and the bad bacteria.

John Alverdy: Well, okay, how about selective use?

Nothing selective.

John Alverdy: And it's a one-size-fits-all to everybody.

John Alverdy: I call it, in the United States, we use a drug called cephalosporins.

John Alverdy: And I call it, it's the cephalo du jour.

whatever it is that day.

John Alverdy: Whatever drug you're using that day, you just use it for everybody.

John Alverdy: Oh, you're doing colon surgery?

Well, everybody gets this cephalo du jour.

John Alverdy: Oh, you're doing stomach surgery?

Well, everybody gets this cephalo du jour.

John Alverdy: And remember, at least in the United States, there's 100,000 elective operations done every day.

John Alverdy: And every one of those patients gets an antibiotic.

John Alverdy: So you start to think 100,000 every day times 365 days.

John Alverdy: And so we live in a world of human progress where we have antibiotics, John Alverdy: but we are probably overusing them.

John Alverdy: And yet we don't know how to stop.

Siobhan McCormack: So if we go back to our patient, let's call him Harry, you know, Siobhan McCormack: we're scrubbing up, you're showing me how to do it beautifully, Siobhan McCormack: everyone is using aseptic techniques.

Siobhan McCormack: What has he had before, just before and during the operation to reduce his chances of infection?

John Alverdy: You brought this point up before, and it's been shown to be very important that, John Alverdy: the anxiety the night before, you know, we always say, get a good night's sleep John Alverdy: and don't eat or drink anything after midnight.

Right.

John Alverdy: Well, imagine you're about to get cut open.

You know it's going to hurt.

John Alverdy: You're going to have pain.

You don't know what the doctor is going to find, John Alverdy: the surgeon is going to find.

John Alverdy: And you're hoping they just find what was seen on the imaging studies, John Alverdy: that the tumor is localized.

John Alverdy: And you have all that.

And, you know, I ask my patients, how'd you sleep last John Alverdy: night?

Most of them say, I didn't sleep at all.

What are you talking about?

John Alverdy: I had to be here at 6 o'clock in the morning.

John Alverdy: How could I sleep?

I woke up at 4 o'clock to drive an hour and a half to get to the hospital.

John Alverdy: And so there's that element that plays a role.

John Alverdy: And if you're doing a bowel prep, which means they drink that stuff, John Alverdy: we call it go lightly.

It's polyethylene glycol.

John Alverdy: They're up all night pooping.

you know John Alverdy: it just doesn't stop you know that we say start drinking at you know 12 or 2 John Alverdy: o'clock in the afternoon and then they're still pooping way into midnight 1 John Alverdy: o'clock in the morning they might feel an urge and go and so nobody gets any John Alverdy: sleep and then they can't eat and they're hungry and they can't eat the you John Alverdy: know they can't have breakfast, John Alverdy: if they're having surgery between 6 and 9 o'clock in the morning and so.

John Alverdy: This is a very stressed individual whose microbiome has been altered by the John Alverdy: bowel prep, by the use of antibiotics, by the prep and draping.

John Alverdy: We decontaminate the skin.

John Alverdy: You're like, what do you decontaminate the skin of?

John Alverdy: Everything.

What do you use?

John Alverdy: Iodine, chlorhexidine, alcohol, whatever we can get our hands on that will just John Alverdy: kill everything.

Do you want to kill everything?

John Alverdy: Well, I want to kill the good guys and the bad guys, and I don't know who's John Alverdy: good or bad, so I kill everything.

It's kind of like war.

John Alverdy: You know, unfortunately, there's going to be collateral damage.

Siobhan McCormack: So if we go to, I mean, the aim is to reduce surgical site infections and anastomotic Siobhan McCormack: leaks in a colorectal operation like this.

Siobhan McCormack: What would be the rates of surgical site infection and anastomotic leaks?

Siobhan McCormack: Because there's quite a wide variation.

John Alverdy: Yes.

So I always say that if a famous hospital, John Alverdy: either in the United States or in the United kingdom could stand up and go, John Alverdy: we have the lowest infection rate of any operation involving the colorectal, John Alverdy: they would do it in a minute.

John Alverdy: It'd be the best marketing campaign ever.

And nobody can do it.

John Alverdy: And because if you have surgery, if you have colorectal surgery in the UK or John Alverdy: in the United States, the first thing the surgeon will do is give you an informed John Alverdy: consent.

We'll say, okay.

John Alverdy: You know, the chances of you having an anastomotic leak are low, but they're not zero.

John Alverdy: And they're somewhere in the literature between 5% and 10%.

John Alverdy: And you're like, well, can't you pick the surgeon that, you know, John Alverdy: has the lowest, you know, anastomotic leak rate?

John Alverdy: No, because no surgeon is immune.

John Alverdy: And most surgeons don't want to count their anastomosis leaks.

John Alverdy: They want to forget them.

Siobhan McCormack: Why do surgeons dread anastomotic leaks and they don't dread surgical site infections in the same way?

John Alverdy: Yeah, because a surgical site infection usually is superficial.

John Alverdy: And over 90% of the time, it can be treated without doing surgery.

John Alverdy: You can open the wound up a little bit.

John Alverdy: You can clean it up, put a wick in there, give some antibiotics, and you're done.

John Alverdy: We call all surgical site infections about 10%.

John Alverdy: Most of them are superficial.

A few are what are called deep organ space infections, John Alverdy: where around the area that you operated on, the cavity, the lung, John Alverdy: the pleural cavity, or the abdominal cavity, there is an abscess.

John Alverdy: And it's usually next to the area that you operated on.

John Alverdy: And that's called an organ space infection, deep, you know, next to an organ.

John Alverdy: And that usually has to do with something not healing properly.

John Alverdy: Because just think of all the operations you do.

You say, well, don't spill anything.

John Alverdy: Just be careful.

And you're like, oh, so the infections only occur when the John Alverdy: surgeon wasn't careful.

No, not true.

John Alverdy: So, you mean they occur even when they're careful?

Yes.

So, can a surgeon predict John Alverdy: which patient is going to develop a leak or an infection?

They can't.

And it's been studied.

John Alverdy: There's a study from the Netherlands where they said to the surgeon, John Alverdy: you know your patient, they're 85 years old, we'll call them hairy, John Alverdy: you know what you've done, it took you four hours, you did a bowel prep, you did everything.

John Alverdy: You tell me on a probability scale of 0% to 100% what you think the chances of a leak are.

John Alverdy: And they correlated it.

They documented it.

John Alverdy: And the surgeon, oh, this patient's 85, diabetic.

This case took four hours.

John Alverdy: I spilled all this crap.

This one's going to leak.

Didn't leak.

John Alverdy: They were wrong more than they were right.

John Alverdy: And so the ability to predict, you know, is always with hindsight bias baked into it.

John Alverdy: In other words, the surgeon, when they have a leak, they'll be like, John Alverdy: I knew that patient was going to leak.

John Alverdy: I knew they were going to leak.

They're 85 years old.

It took forever.

John Alverdy: I knew this was going to happen.

John Alverdy: And they forgot all the times they operated on an 85-year-old in the same circumstances John Alverdy: that did not leak or did not develop an infection.

We call that confirmation bias.

John Alverdy: You confirm your own bias by looking at things in hindsight.

John Alverdy: And we all do it.

You know, we can't.

John Alverdy: We're human beings.

We make judgment errors.

Siobhan McCormack: Well, I mean, reading around the subject, this will be known to you, Siobhan McCormack: but I found it astounding, and I think the listeners will as well.

Siobhan McCormack: The most sort of post-colorectal surgery, surgical site infections, Siobhan McCormack: originate from the patient's own gut?

John Alverdy: Well, I would say we don't know today which are due to external contamination John Alverdy: and which are due to internal or the patient's own flora contamination.

John Alverdy: We don't know because, you know, I'll give you an example.

John Alverdy: If your patient develops clostridium difficile infection and it happens to be John Alverdy: on the nurse's fingers or on the sink, John Alverdy: an infectious disease specialist will say, well, John Alverdy: your patient got multiple antibiotics and the nurse gave it to the patient.

John Alverdy: I'm like, how do you know the patient didn't give it to the nurse?

John Alverdy: And they're like, well, it's logical.

John Alverdy: Was on the nurse's fingernails, it was on the sink.

So I'm like, John Alverdy: maybe the patient put it on the sink.

John Alverdy: Maybe the patient put it on the, no, no, no, it's, it's, we know.

How do you know?

John Alverdy: Did you have a baseline DNA fingerprint of that bacterial strain in that patient John Alverdy: before this happened and after?

And they're like, no.

John Alverdy: So you didn't vectorially detect this.

John Alverdy: You know, you didn't go from person A to person B and have the baseline DNA fingerprint first.

John Alverdy: You're like, well, that would be hugely labor intensive.

Yes, John Alverdy: but that's the challenge for the next 20 to 30 to 50 years is somebody will do that.

Siobhan McCormack: And you reminded me of crime scene investigations and evidence and will it hold Siobhan McCormack: up in court, which is kind of really interesting.

Siobhan McCormack: Let's move on to this subject, which I find amazing.

Siobhan McCormack: Why is a colorectal surgeon also doing research into microbiome science?

Siobhan McCormack: So when did that happen in your career trajectory?

Siobhan McCormack: And was it even microbiome science then, or was it just microbiology?

John Alverdy: Yeah, I don't want to mislead the viewers here that I'm a colorectal surgeon.

John Alverdy: I'm a gastrointestinal surgeon.

I've done colorectal surgery.

John Alverdy: In the United States, there is a special board and a special fellowship for colorectal surgery.

John Alverdy: But I've done plenty of colorectal surgery over the course of my career.

John Alverdy: Um, but, um, what happened was I was studying the gut microbiome and bacterial virulence in general.

John Alverdy: And this woman who was a surgery resident wanted to come into my lab and she John Alverdy: wanted to go into colorectal surgery, do a fellowship after her general surgery training.

John Alverdy: And, um, she said, I want to work in your laboratory, but I want to be a colorectal surgeon, John Alverdy: and I want to study anastomotic leak, could we come up with a hypothesis that John Alverdy: would allow me to study this?

John Alverdy: And I said, of course, we'll frame anastomotic leak as an infection, John Alverdy: not as a technical error.

John Alverdy: And we'll prove it.

And she did the first study.

John Alverdy: Andrea Olivas, She did an amazing study where she took large rats, John Alverdy: did preoperative radiation on them to create sort of a field effect of radiation, John Alverdy: then did the anastomosis.

John Alverdy: And then contaminated that anastomosis with a bacterium that we knew had the John Alverdy: capacity to make this collagenase enzyme that eats through the tissue.

John Alverdy: And she proved the hypothesis.

John Alverdy: She proved it was not an error in surgical technique, that it was due to the microbe, John Alverdy: expressing this gene that made this gene product, this protein, John Alverdy: collagenase, which bound to the tissues, John Alverdy: ate through the tissues, and caused the leak.

John Alverdy: Sort of unambiguously, uncontestably, she proved it.

Siobhan McCormack: So just going back to help the listeners, because this is really important.

Siobhan McCormack: So when you're cutting through, you need wound healing afterwards.

Siobhan McCormack: And the laying down of collagen is a hugely important part of that.

Siobhan McCormack: And also your immune system to recover from wounds and to heal properly.

Siobhan McCormack: So you're saying that there are certain bacteria that are found in the gut that produce an enzyme, Siobhan McCormack: called collagenase which actually cuts through Siobhan McCormack: enzymically the collagen that's being laid down Siobhan McCormack: so it's almost undoing all your work if you Siobhan McCormack: like and these collagenases are found Siobhan McCormack: in in pathogenic bacteria which Siobhan McCormack: are part of the the normal commensal Siobhan McCormack: in the gut when in surgery Siobhan McCormack: if you're sort of giving people lots of antibiotics you alter the balance so Siobhan McCormack: these guys are kind of more uh there's more growth uh they're more um formidable Siobhan McCormack: they're the ones uh have this enzyme so obviously you don't want them around Siobhan McCormack: in large amounts when you're trying to heal because they're We're doing the opposite.

John Alverdy: That's correct.

I mean, I think you got the story exactly correct.

John Alverdy: And remember that, you know, I call them flesh eating bacteria because I think John Alverdy: the lay public understands that.

John Alverdy: Oh, I don't want to get one of those flesh eaters that will eat my face off John Alverdy: or take my arm off.

I, you know, I got to avoid that if I cut myself.

John Alverdy: You know, just imagine this, and you might know this, Shiv.

John Alverdy: You know, if you cut yourself in the garden, John Alverdy: and you go to the emergency room and say, I cut myself and it's really deep, John Alverdy: they're going to irrigate it and give you antibiotics.

No question.

John Alverdy: And you might say, how many people that cut themselves actually go and get the John Alverdy: antibiotics versus those that go to the doctor, to the hospital, John Alverdy: and get the antibiotics?

What is that balance?

John Alverdy: And to what extent are those antibiotics necessary?

John Alverdy: And you don't know the answer because you'd have to get all the people that John Alverdy: cut themselves in their garden deeply, and you'd have to find them that did John Alverdy: not go to the doctor and did not get antibiotics versus those that did and look at the infection rates.

John Alverdy: And, you know, I just look in my neighborhood and I think of all the gardeners John Alverdy: I see around here and I'm like, I am sure people have cut themselves deeply John Alverdy: many times and have not gone to the doctor and not received antibiotics and healed perfectly fine.

John Alverdy: So what constitutes who's at risk and who isn't?

John Alverdy: But in medical practice, I call this guilty knowledge.

John Alverdy: You're the doctor, you're in the emergency room, you have guilty knowledge.

John Alverdy: Here's a person who came in, they got a big cut, you're like, John Alverdy: okay, let's irrigate it and give you antibiotics and a tetanus shot.

John Alverdy: Why?

Because I know you came to me, and that's at risk.

John Alverdy: And so I need to do something for you, not nothing.

Siobhan McCormack: Okay, let's break that down a bit.

So, okay, there's the medico-legal aspect.

Siobhan McCormack: So you kind of, you never get sued for doing something.

Siobhan McCormack: Even, you know, you will get sued for not doing something.

So you kind of think, Siobhan McCormack: if in doubt, do something.

Siobhan McCormack: So there's that pressure.

There's also the pressure of social norms.

Siobhan McCormack: So we're still in that kind of germ theory of disease.

Antibiotics are amazing.

Siobhan McCormack: And, you know, my doctor didn't take me seriously.

So there always is that kind of worry.

Siobhan McCormack: And I suppose for a while in the 80s and Siobhan McCormack: 90s it was look it's not going to do any harm but all Siobhan McCormack: that has changed now because and i Siobhan McCormack: think it's going to be interesting when the first case of Siobhan McCormack: you know that actually you do Siobhan McCormack: did you inform your patient that it could alter their microbiome they Siobhan McCormack: have you know had their they can prove that they've had sort Siobhan McCormack: of pre-antibiotic post-antibiotic stool samples and they Siobhan McCormack: you wreck their microbiome that's going to be a very Siobhan McCormack: interesting thing so i want to sort of go Siobhan McCormack: back a few steps we talked about your the operating room Siobhan McCormack: uh we talked about your team and how important Siobhan McCormack: they are and how most important person in the room is Siobhan McCormack: the the patient but there is another team i Siobhan McCormack: want to talk about now um who is incredibly important and that's the the team Siobhan McCormack: of microbes in your gut um this incredible uh sort of facility that we have Siobhan McCormack: who can help us heal after you've done your job and you've closed up, Siobhan McCormack: you need this team to be the best quality possible.

Siobhan McCormack: And I just want to talk through that a bit, because I don't know if people understand Siobhan McCormack: how important it is when your immune systems is needed and when you're healing from wounds.

Siobhan McCormack: I mean, what do we know about that in terms of wound healing?

John Alverdy: Dr.

Yeah, that's a great question.

We've just published a paper in Nature Microbiology John Alverdy: that asked that very question.

John Alverdy: If you infect a mouse...

John Alverdy: That is genetically, all these mice, we infected 20 or 30 of them, John Alverdy: they're all the same genetic background.

John Alverdy: Do they fight the infection better with their microbiome or worse with their microbiome?

John Alverdy: So we gave them antibiotics, infected them, and many died.

John Alverdy: And the ones that we kept their microbiome intact survived better.

John Alverdy: And the ones that we decontaminated and then gave a fecal transplant to did John Alverdy: as well as the ones with an intact microbiome.

John Alverdy: So we then discovered that a metabolite in the gut that is produced by the normal microbiota, John Alverdy: these indoles, they're called, they're from eating tryptophan, which your microbiome.

John Alverdy: Metabolizes to indoles.

John Alverdy: Those bind to the aryl hydrocarbon receptor on macrophages and turn on these John Alverdy: macrophages to be a little bit more immune activating.

John Alverdy: And so all of a sudden, you now see the molecular pathways by which having an John Alverdy: attacked microbiome can activate your immune system to make you not only fight John Alverdy: infection better, but heal better.

John Alverdy: So now, to your point, you're better off with a normal microbiome than a not a normal microbiome.

John Alverdy: However, you're coming to the operating theater with a disease.

John Alverdy: And you're coming to the operating theater maybe having received chemotherapy John Alverdy: and radiation.

And you're coming to the operating theater and you're going to get antibiotics.

John Alverdy: And you're going to get everything decontaminated and you're going to get everything sterilized.

John Alverdy: And so all of a sudden, the team that you talk about is being indiscriminately destroyed.

John Alverdy: Because going back to the 1920s, we thought, you know, the only good germ is a dead germ.

John Alverdy: You know it's i stole that John Alverdy: line probably from some general in the John Alverdy: army or something like that you know uh John Alverdy: you know or at least in america we used to say the only the only John Alverdy: good indian is a dead indian you know because they John Alverdy: were the they were the foe and you know we were colonizing this country and John Alverdy: so but that was wrong and and this is probably this idea has been good up to John Alverdy: this point but you've made this point before Shiv it's probably not, John Alverdy: the path we're going to take in the future we're going to try to be more.

John Alverdy: Selective.

And that's why there are, in many battles between friend and foe, there are, John Alverdy: methods to be more selective in getting at the pathogenic, the bad actors, John Alverdy: if you will.

And we don't know how to do that yet.

John Alverdy: And so I like to think of the microbiome as just, to your point, John Alverdy: a team that we need to understand.

John Alverdy: And how wonderful would it be if we could take that patient, John Alverdy: Harry, that you talked about, this 43-year-old, and we could understand who John Alverdy: is friend and who is foe in there before we operate.

John Alverdy: You're like, well, that would take a lot of time and money, right?

John Alverdy: Yeah.

Do we do that now?

No.

John Alverdy: Should we do that?

Maybe.

John Alverdy: And what are the two most important things that affect the microbiome?

Diet, antibiotics.

John Alverdy: Are we concerned about those?

No.

Antibiotics for everybody?

John Alverdy: I don't care what diet you're on.

You've got a cancer.

I've got to get at that thing.

John Alverdy: Wait a minute.

Let's take a step back here and think about how we might modulate those two things, John Alverdy: those two major advances that got us from the early 1900s to today and maybe John Alverdy: be a little more selective.

John Alverdy: And, you know, scientists hate when you anthropomorphize an argument.

John Alverdy: You turn an argument into, you know, something that involves a human interaction.

John Alverdy: But, you know, war is no different.

Everyone would like the innocent civilians John Alverdy: not to be killed and only the bad actors to be killed.

John Alverdy: And it's very hard.

How do you preserve the lives of the innocents and just John Alverdy: get the bad guys to be eliminated.

That's no easy task.

John Alverdy: And it's the same with the microbiome.

Siobhan McCormack: Okay, well, I'm going to add another sociopolitical element to it, Siobhan McCormack: because there's this idea that there are good guys and bad guys in your gut.

Siobhan McCormack: And as you know, you've got these microbes, mostly bacteria, in a well-balanced gut.

Siobhan McCormack: You may have potential pathogens who just are harmless.

Siobhan McCormack: Then we talk about what turns a disinterested bacteria into a potential pathogen Siobhan McCormack: that can do you harm when other times in your life, it's just sat there doing Siobhan McCormack: nothing and not causing any problems.

Siobhan McCormack: And even more interestingly, has benefits in certain conditions.

Siobhan McCormack: And then we get to this kind of really complex idea.

There's lots of contextual nuances here.

Siobhan McCormack: And yet, I kind of always draw on the idea that we're used to watching really Siobhan McCormack: complex detective movies or really complex box sets on Netflix, Siobhan McCormack: which really do show the complexities of any social group.

Siobhan McCormack: And I suppose these are Earth's earliest inhabitants, these bacteria, Siobhan McCormack: Earth's earliest social groups.

Siobhan McCormack: And they do reflect a lot of our behaviour.

Siobhan McCormack: We've got cooperation in form of cross-feeding, you've got growth, Siobhan McCormack: you've got virulence, you've got competition for resources, the competitive Siobhan McCormack: marketplace, if you like.

Siobhan McCormack: You've got rules, it's dynamic, they're responsive, they're Siobhan McCormack: interactive they they create beautiful architectural Siobhan McCormack: structures called biofilms you know the Siobhan McCormack: the analogies go on and i just Siobhan McCormack: i suppose when i'm talking about this to patients Siobhan McCormack: i do use a lot of these potentially annoying to scientists analogies because Siobhan McCormack: you have to explain in in in ways that people understand um and you know if Siobhan McCormack: you start talking about receptors and the molecular mechanisms then they kind Siobhan McCormack: of fade off and it doesn't seem relevant.

Siobhan McCormack: I suppose we use this language to try and make it relevant to them but it makes Siobhan McCormack: it relevant to me as well because it helps me Siobhan McCormack: kind of understand it's a good way to to get a grip of the science so if you're Siobhan McCormack: talking about harry's you know the city in his gut microbiome that has these Siobhan McCormack: living you know bacteria and we want him to have the best workforce he can to Siobhan McCormack: help him recover from the operation.

Siobhan McCormack: Surely if he's been eating a terrible diet for years and he's where he is now Siobhan McCormack: is it not just too late for him to make dietary changes a week or two weeks Siobhan McCormack: or three weeks before the operation.

Siobhan McCormack: Because I think people would find it incredibly empowering, but most doctors, Siobhan McCormack: most surgeons would say, ah, you know what?

Siobhan McCormack: It's not going to make any difference now.

He is where he is.

Don't make him feel bad.

Siobhan McCormack: Don't make him feel it's his fault, which it clearly isn't and wouldn't want Siobhan McCormack: to do that.

How potent is changing the diet pre-operatively?

John Alverdy: Yeah, that's a great point.

and actually this guy, Harry Flint, John Alverdy: he's originally from Scotland and he came to visit from the University of Chicago and he's retired now.

John Alverdy: And I showed him some data that we had in mice where we put mice on a Western John Alverdy: diet and they did very badly.

John Alverdy: They had a high complication rate after surgery.

Siobhan McCormack: So you gave them a sort of junk food diet, you did colorectal surgery equivalent Siobhan McCormack: on them And then afterwards, you found what they had a high rate of surgical Siobhan McCormack: site infections and leak.

John Alverdy: Yes.

Siobhan McCormack: Compared with mice who were on a plant-based diet or what would it be, chow?

John Alverdy: Yeah.

So mice eat what's called mouse chow and rats eat what is called rat chow.

John Alverdy: And here's what rat chow and mouse chow is.

John Alverdy: High fiber, no meat, low fat fat.

John Alverdy: All the goodies in it.

And you're like, who eats like that?

Nobody.

I know.

John Alverdy: I don't know anybody, myself included.

Last night I ate pizza.

John Alverdy: I mean, that was not high fiber, low fat.

In fact, it had some sausage on it.

John Alverdy: So, but Harry Flint told me this.

John Alverdy: He said, you can change that mouse's microbiome in two days.

John Alverdy: Back to normal.

I'm like, but the mouse was eating this junk food diet, John Alverdy: to your point, for almost two months.

John Alverdy: And he goes, two days.

And he was right.

We wrote that.

We published that paper John Alverdy: in British Journal of Surgery.

John Alverdy: And he was absolutely right.

We did all the microbiome analysis.

John Alverdy: And it takes almost no time to shift your microbiome back to a normal state, John Alverdy: a near normal state with food.

John Alverdy: Almost no time.

And that's the point you're trying to make, Shiv, John Alverdy: which is, well, if somebody's been eating bad for 40 years, you're not going John Alverdy: to fix that in two days.

Yes, you are.

John Alverdy: In terms of microbiome composition and microbiome function, now, John Alverdy: maybe you're not going to reshape their diabetes and reshape their hypertension John Alverdy: and reshape all the other systems that have been done.

John Alverdy: But you certainly are going to change the metabolomic, the metabolites that John Alverdy: that gut microbiome produces that activate the immune system, John Alverdy: that boost it, to use your point.

John Alverdy: And you certainly are going to shape its composition, its team composition.

Siobhan McCormack: Yeah.

I mean, the David paper where they sort of do a radical change in diet in a human study.

Siobhan McCormack: And I think it was in three or even in 24 hours for some of them.

Siobhan McCormack: But they talk about three to five days.

if you radically change your diet you Siobhan McCormack: radically change the composition and I know that people will argue well you Siobhan McCormack: know you have to test out whether that alters the function but I suppose I'm Siobhan McCormack: also thinking Sheena Fraser, my microbiome.

Siobhan McCormack: Co-host and partner in this endeavor.

Siobhan McCormack: I mean, we always kind of think everyone talks about, well, you know, Siobhan McCormack: you don't know that, but we've got to kind of put it in balance with the overall picture.

Siobhan McCormack: I mean, we're talking fruit, veg and legumes here.

Siobhan McCormack: We're not talking about chemotherapy with, you know, incredible side effects.

Siobhan McCormack: And in fact, the only side effects would be, you know, positive ones.

Siobhan McCormack: Okay, maybe it won't help with this operation, but it may, if they alter their Siobhan McCormack: diet like this long term, it will alter their metabolic or improve their metabolic Siobhan McCormack: health, their cancer risk, their cardiovascular risk and so on.

Siobhan McCormack: So no one, I don't know, I'm a bit confused about how we look at the evidence Siobhan McCormack: because as a general practitioner, I have completely ignored research.

Siobhan McCormack: I just wait for guidelines to come out.

Siobhan McCormack: The National Institute of Clinical Excellence, is it in the guidelines?

No, I'm not interested.

Siobhan McCormack: Until I'm now back at uni doing a master's in nutritional medicine.

Siobhan McCormack: And my mind is like, you know, exploding with the complexity of it all and what Siobhan McCormack: you guys are trying to do.

Siobhan McCormack: And so I'm changing my opinion now.

Siobhan McCormack: We have to look at when we're talking about, you know, do no harm, Siobhan McCormack: but we have to also talk about what's the best available evidence for the patient in front of us.

Siobhan McCormack: And if we're sort of putting on blinkers and refusing to look at the totality Siobhan McCormack: of the evidence, unless it's in guidelines, which can take, I don't know, Siobhan McCormack: they say 17 years for something to move from the lab to guidelines, Siobhan McCormack: then that's not going to help the patient in front of me now.

Siobhan McCormack: So how do we change that?

Siobhan McCormack: I mean, you're someone who's looking at the evidence from all angles, Siobhan McCormack: but I'm guessing that clinicians that you know and surgeons that you know are Siobhan McCormack: not able to spend the time looking deeply into the evidence in in vivo studies Siobhan McCormack: on animals and in vitro studies and collate it all together.

Dr.

John Alverdy: These are all excellent points.

And, you know, again, you're faced with the patient.

John Alverdy: Remember that, and you know this as a practitioner, you know, John Alverdy: patients will do anything you tell them to reduce their risk of a bad outcome.

If you said to them.

John Alverdy: You know, you can actually reduce your risk of getting a postoperative infection John Alverdy: if you go on this diet and maintain it afterwards.

John Alverdy: In fact, one of my colleagues, Ben Shogan, who spent two years in my lab, John Alverdy: he actually wrote the paper in Science Translational Medicine on the collagenase gene.

John Alverdy: He is a colorectal.

He trained at the Mayo Clinic to be a colorectal surgeon.

John Alverdy: He has his own laboratory at the University of Chicago, very close to my laboratory.

John Alverdy: And he has really exciting evidence that your cancer recurs.

John Alverdy: So you do a colorectal cancer and it's curative, and you're like, John Alverdy: I nailed it.

The margins are clean.

John Alverdy: The CAT scan looks good.

your chances of recurrence five years later are dependent John Alverdy: on whether you harbor one of these bugs in your GI tract.

And you're like, John Alverdy: well, we gave antibiotics.

John Alverdy: We killed that thing.

It's antibiotic resistant.

John Alverdy: The one that makes the collagenase in those patients that develop a recurrence John Alverdy: are the ones that are antibiotic resistant, both by genetic means.

John Alverdy: So we do PCR are to see that they carry that gene.

John Alverdy: And we do culture, you know, where you put it, you know, have antibiotic discs.

John Alverdy: And you can see that the antibiotic you used during surgery didn't kill the John Alverdy: germ you wanted, you hoped it would.

John Alverdy: And that germ persists in a small group of patients, and they go on to develop a recurrence.

John Alverdy: Well, if you told a patient, you, Shiv, said, well, I know you've had the surgery, John Alverdy: and things went well, and your pathology report looks great, John Alverdy: and the surgeon's all excited and you didn't leak but you know you're still John Alverdy: at risk for a recurrence in five years, John Alverdy: and you can reduce your recurrence if you'd lose some weight and maybe shift your diet, John Alverdy: and maybe let nature push this bad bug out of you by building up your microbiome having more, John Alverdy: I call the good guys in the microbiome, they have home field advantage You can John Alverdy: build up your normal microbiome with diet and avoidance of antibiotics and push this bad actor out.

John Alverdy: You know, I know we haven't talked about virulence yet, but remember that people John Alverdy: talk about humans having the killer instinct.

John Alverdy: These are the circumstances that we probably put some bacteria under.

John Alverdy: These are the environmental cues that we expose certain bacteria that behave nicely in the sandpit.

John Alverdy: And we put them in an environment in which they're forced.

John Alverdy: So just think about this for a minute.

anxiety, no food after midnight, John Alverdy: a boatload of antibiotics.

Now, how about some opioids?

John Alverdy: How about some morphine, a little after surgery?

And by the way, John Alverdy: don't eat or drink till you poop.

John Alverdy: Okay, so we're going to starve you.

And they're like, hey, my only way out is to kill this host.

John Alverdy: And if I kill this host, maybe a bird will eat its carcass and I can jump to John Alverdy: a new host.

I don't know.

I'm making this stuff up.

John Alverdy: But, you know, that's kind of how you might conceptualize this and say, John Alverdy: look, you know, we don't know all, we don't have all the answers.

John Alverdy: I know you like an agonist, a receptor, and a drug that blocks it.

John Alverdy: And here, take this PPI or take this thing and this will work.

John Alverdy: We like that idea.

It's nice and clean.

John Alverdy: And, you know, you give it to patients, you do a clinical trial and it works for whatever it is.

John Alverdy: But we're now dealing with a social group, a team.

John Alverdy: And I like to think of the microbiome as just another gene pool.

John Alverdy: It's just another set of molecules and genes that we have to account for, which we didn't before.

Siobhan McCormack: Okay.

So I like to think of it as a team that you have to look after.

Siobhan McCormack: So if you have this workforce within you you have to pay fair wages you have Siobhan McCormack: to feed them you have to and if you do you will get so much back and if you Siobhan McCormack: don't and all those beneficial microbes kind of die out then you're left with Siobhan McCormack: potential pathogens so it's a kind of no-brainer for me that, Siobhan McCormack: you know what do they eat they might plant fiber to make these short-chain fatty Siobhan McCormack: acids that are so important in post-operative recovery and in a myriad of ways Siobhan McCormack: which we don't have time to go into.

But.

Siobhan McCormack: It's just sort of changing.

I don't know what hospital food is like at your Siobhan McCormack: hospitals, maybe the same as the NHS.

Siobhan McCormack: You're looking, and look from the expression on your face, it's not, Siobhan McCormack: you're not kind of talking, you know, beautiful plant, whole food, plant-based diets.

Siobhan McCormack: But this is incredibly important when you think of how much money and expense Siobhan McCormack: into research that many of your colleagues are looking into tiny areas, Siobhan McCormack: tiny receptors that may have a very small effect on reducing surgical outside infections.

Siobhan McCormack: And then you've got this, the low-lying fruit, you know, basically what you eat.

Siobhan McCormack: And there was one quote, I was trying to find it this morning in one of your Siobhan McCormack: papers that kind of really resonated with me, because you said, Siobhan McCormack: out of all the ways we can modulate the gut microbiomes, you're talking biotics, Siobhan McCormack: antibiotics, probiotics, prebiotics, symbiotics, Siobhan McCormack: postbiotics, and even FMT, although there's some interesting research being done in that area.

Siobhan McCormack: You said the one, something I'll paraphrase, the most potent, Siobhan McCormack: affordable, available, acceptable, you know, an equal way to alter your gut microbiome is diet.

Siobhan McCormack: And I just thought, wow, you've got a gut microbiome researcher of many decades Siobhan McCormack: and a surgeon and that seems crazy and that no one's really grabbing that.

Siobhan McCormack: I mean, And Sheena and I just want to get going with that now.

John Alverdy: Yeah, I think it's great.

You know, I got to tell you that James Kinross, John Alverdy: he's a brilliant, brilliant guy and studies the microbiome.

John Alverdy: And he invited me to give a talk in London.

John Alverdy: And then this guy got up, who was a PhD researcher, and he took these rats and John Alverdy: he did these horrible things, gave him nitrogen, mustard.

John Alverdy: I can't remember what he did.

He did some horrible thing.

And the rats all developed John Alverdy: cancer, or many of them developed cancer.

John Alverdy: And then he put walnuts in the cage and then did all these horrible things and John Alverdy: none of them developed cancer.

John Alverdy: And I'm thinking, this is what people want.

This is why the probiotic industry is so hot now.

John Alverdy: I want to eat pizza, hamburgers, and french fries, but I want to take a probiotic John Alverdy: pill the day before surgery and it to cure me.

John Alverdy: And surgeons, unfortunately, are the same way.

John Alverdy: CAT scan, tumor, me, trained, I can take it out.

John Alverdy: And you're like, wait a minute, hold on, cowboy, cowgirl.

John Alverdy: That's not exactly correct.

Maybe there's things as an internist we can do that John Alverdy: can change the course and outcome.

John Alverdy: And they're like, nah, what are you going to do?

Give this person walnuts for John Alverdy: three days?

It ain't going to make a difference.

John Alverdy: And it might.

And that's why you're right.

John Alverdy: The public doesn't like this idea of it's complex and team.

We have to understand John Alverdy: it better.

But the future is coming.

John Alverdy: It's here, maybe, where we can assess the microbiome in that cancer patient.

John Alverdy: And you're hairy of 43 years old and say, you got a couple of bad actors in John Alverdy: there.

you don't want there during surgery.

John Alverdy: And let's delay things for a couple of weeks and put you on this diet.

John Alverdy: And then let's re-interrogate your microbiome and see if we can eliminate them John Alverdy: and make it and put it in better shape.

John Alverdy: Can't change your hemoglobin A1c.

John Alverdy: You know, I can't change your blood pressure yet.

John Alverdy: But in the next five years, this is a wake-up call.

John Alverdy: You're having major surgery and you've got to stay on this diet.

John Alverdy: You've got to lose weight.

You've got to get those things back in shape.

John Alverdy: Otherwise, all the surgery that was done is not going to do you any good.

John Alverdy: And that's exciting because it's something you can modulate.

John Alverdy: And it's the simplest thing in the world.

But like anything else in medicine, John Alverdy: at least, you know, in the United States, for example, John Alverdy: imagine if it's proven that dietary prehabilitation can shift your microbiome John Alverdy: and benefit you in terms of infection rate and in terms of cancer recurrence.

John Alverdy: Imagine if it were to for a moment.

John Alverdy: Who would have to pay for that two weeks of dietary rehabilitation?

John Alverdy: The insurance companies.

John Alverdy: They don't want to pay right now.

Maybe the National Health Service doesn't John Alverdy: want to pay also because you're going to delay surgery for two weeks.

John Alverdy: It's going to cost X amount of money.

John Alverdy: It's going to increase costs.

But, you know, I like to think of truth as being John Alverdy: invincible in its own way.

John Alverdy: If it's true, it needs to be done.

John Alverdy: And, you know, you say, oh, I used to wait for the guidelines and stuff, John Alverdy: but now you're like looking going, you know, there's a lot of science behind John Alverdy: this and it all makes kind of sense.

Siobhan McCormack: If all the arrows are pointing in the same direction, and I suppose the best Siobhan McCormack: available evidence for any listeners out there who are, you know, Siobhan McCormack: contemplating or having surgery of any sort, really, then getting, Siobhan McCormack: you've got nothing to lose by getting your gut microbiome in good shape.

Siobhan McCormack: You know, it's really empowering.

It's really exciting.

Siobhan McCormack: What's the worst that can happen?

There is really no particular downside.

Siobhan McCormack: Getting those whole food, plant-based foods in and cutting out the things that Siobhan McCormack: we know are detrimental to the biome.

Siobhan McCormack: That's the emulsifiers, the additives.

Siobhan McCormack: So all those ultra-processed foods.

Siobhan McCormack: So it's not just what you do have, it's what you emit as well.

Siobhan McCormack: You know, let's get most people in good shape using what is available.

Siobhan McCormack: I kind of think it's exciting.

John Alverdy: It is exciting, but it's also very challenging, in my opinion, John Alverdy: for the primary care physician, the general internist, to be able to change John Alverdy: behavior because, you know, in your own practice, you know, getting people to John Alverdy: quit smoking and to lose weight and to change their diets, not so easy.

John Alverdy: And it's very tempting to think you can modify these things and yet they're John Alverdy: not so easily modifiable.

John Alverdy: You know, there's a, you know, I wrote a paper about U-curves, John Alverdy: Laffer curves and U-curves and, you know, and there's a lot of interest in, John Alverdy: you know, how human progress has gotten us to this point where we're here.

John Alverdy: But if we keep going, human progress, Let's have more plastic in the ocean, more garbage.

John Alverdy: Let's use antibiotics more.

If some is good, more is better.

John Alverdy: Let's get more processed food.

Let's get more McDonald's on every street corner around the world.

John Alverdy: Let's all get fatter because, you know, let's all drink more.

John Alverdy: All of a sudden, you're like, wait a minute.

John Alverdy: We've made all this progress, and now the curve's going back up where we're John Alverdy: seeing we came down a little bit and now we're going back the wrong way because...

John Alverdy: We haven't paid attention to nature-inspired design.

John Alverdy: To what extent can we destroy the ecology of the GI tract with our current methods?

John Alverdy: And when will it bite us back?

Siobhan McCormack: The striking parallels aren't there between Earth's ecosystem and the issues Siobhan McCormack: we have with reduced biodiversity and global warming and our own planetary, Siobhan McCormack: if you like, ecosystem, which is mainly the gut microbiome, where we also talk Siobhan McCormack: about reduced biodiversity.

Siobhan McCormack: And well climate change could be chronic low-grade inflammation I guess and gut barrier, Siobhan McCormack: permeability issues so yeah yes there's Siobhan McCormack: plenty of parallels there and it's all you know Siobhan McCormack: a lot of it is is based on the the Siobhan McCormack: food supply and agriculture and soil and Siobhan McCormack: how we look after the earth we've kind Siobhan McCormack: of been taught on this sort of pharmacy model which is Siobhan McCormack: the body gets disease and we have to take medicines Siobhan McCormack: and uh yeah it's kind Siobhan McCormack: of i suppose it's been a revelation to me my journey over the Siobhan McCormack: last 10 years looking at you know the lifestyle medicine um research papers Siobhan McCormack: and publications in the last couple of decades and the molecular biology of Siobhan McCormack: what happens when you sleep or don't sleep what happens when you eat certain Siobhan McCormack: things and polyphenols and physical activity and it's incredible what's been Siobhan McCormack: found and yet because there isn't a, Siobhan McCormack: pharmacological, you know, therapeutic agent which you can sell, Siobhan McCormack: it's just not really spoken about so much.

John Alverdy: No, I think you're right.

Let's work on things, to your point, John Alverdy: Shiv, that can maybe shift the microbiome, modulate it in a way that you never John Alverdy: get the disease at the beginning.

John Alverdy: How important would that be?

You know, people survive cancer better.

John Alverdy: We've actually turned it from an acute problem where you get it and you died John Alverdy: to more of a chronic illness.

John Alverdy: But there is...

John Alverdy: No interest, either by industry or at least in the scientific community, in prevention.

John Alverdy: There's not, well, let's say, there's not only say no interest.

John Alverdy: There's less interest in prevention strategies and how they might be owned by the individual.

John Alverdy: You know, you have to have ownership of your own health, to your point.

John Alverdy: And preventing disease.

And maybe that's where they go.

And that's why, John Alverdy: again, television in the United States, John Alverdy: I'm watching all these probiotic commercials, and they help support.

John Alverdy: They've got to be careful with their claims so they don't get sued.

John Alverdy: Helps support your microbiome.

They can't make a claim that changes your microbiome.

John Alverdy: They can't make a claim that it prevents cancer.

John Alverdy: But it helps support.

Please take this.

John Alverdy: And we know that, again, your own microbiome has home field advantage.

You shaped it this way.

John Alverdy: Putting one probiotic down is not going to do anything.

John Alverdy: It's not going to, you know, I want to take a probiotic and eat hamburgers and John Alverdy: french fries all day long.

No, that won't work.

John Alverdy: Stop the hamburgers and french fries.

Move to more of a Mediterranean-type plant-based diet.

John Alverdy: And there's a way to study your microbiome that's using emerging technology.

John Alverdy: One person you might consider talking to is Eugene Chang.

John Alverdy: He's a gastroenterologist, and he is a world-famous figure in the microbiome space.

John Alverdy: He's a close collaborator of mine, and he's developed a 20-panel point-of-care diagnostic.

John Alverdy: To understand what metabolites are being secreted in response to the foods that John Alverdy: you eat or your general health.

John Alverdy: Remember, right now, we do not know how to tell anybody, a doctor or anybody John Alverdy: else, if your microbiome is abnormal or normal.

John Alverdy: But I like to think of moving away from a disease state toward a healthy recovery state.

John Alverdy: I don't like to think of disease healthy because it's too complicated.

John Alverdy: I like to think of moving.

John Alverdy: If I could have a measurement and that I could give to you, Shiv, John Alverdy: and you'd say, I'm going to put your stool on this panel, 20 metabolite panel.

John Alverdy: I'm going to say, you're changing your diet.

You've lost 10 pounds.

Wonderful.

John Alverdy: You're moving away from the disease state toward a more healthy state, John Alverdy: not at a healthy state, but you're moving in the right direction, John Alverdy: you would like that test.

John Alverdy: But you don't want a test where like, well, your tryptophan is up and you're John Alverdy: short-chain fatty.

It's like, you know, it's like, it's too much information.

John Alverdy: You know, and it's too binary.

John Alverdy: Disease, health.

That's not how the world works.

It's sort of like, John Alverdy: You're in an unhealthy place.

I know you've probably been through this with John Alverdy: many of your own patients, but you're in an unhealthy place, John Alverdy: and I need to slowly move you to a more healthy.

John Alverdy: Place in your journey of your own body.

Siobhan McCormack: It is a journey, and it's a dynamic thing, isn't it?

Siobhan McCormack: This idea of health being a destination is kind of ridiculous because, Siobhan McCormack: you know, as you know, we eat the pizza.

Siobhan McCormack: We're not so healthy afterwards.

Then we maybe have a nice salad and then we're in a healthier state.

Siobhan McCormack: So it's this kind of dynamic, ever-moving journey until the end.

Siobhan McCormack: But actually, yeah, I think people just talk about health as one thing.

Siobhan McCormack: Professor John Alverde, you are, you know, it's been incredible talking to you.

Siobhan McCormack: I love your work.

I've been deep diving into your papers for six months.

Siobhan McCormack: My family think I'm a boring, obsessed nerd, but I don't care.

I kind of love it.

Siobhan McCormack: And yeah, thanks so much for your work.

Thank Thank you for spending the time speaking to me.

John Alverdy: It was a pleasure.

Siobhan McCormack: Yeah.

And thank you for letting us come into the operating theater with you.

Siobhan McCormack: And now that you've closed up and Harry is back on the ward and safe in the nurse's care.

John Alverdy: Then I think Harry needs to be in your hands now.

Siobhan McCormack: Oh, right.

John Alverdy: And he needs to be under your care for the next five to 10 years so you can John Alverdy: keep Harry healthy to age.

Siobhan McCormack: Well, I tell you, Sheena and I would love that because we do talk a lot with Siobhan McCormack: patients about this kind of thing.

Siobhan McCormack: And we would like, you know, we'd be talking about exercise and sleep.

Siobhan McCormack: We'd be talking about whole food, plant-based diet, talking about getting rid Siobhan McCormack: of all the emulsifiers and additives.

And I tell you, the patients love it.

Siobhan McCormack: They love it.

They love the, you know, the ecosystem idea.

They get that.

Siobhan McCormack: And they do it in a much easier way than sort of telling them that they're bad Siobhan McCormack: and they should stop eating burgers.

Siobhan McCormack: Kind of, you know, feed your ecosystem.

And that kind of works.

Siobhan McCormack: Excellent.

All right.

Well, safe journey.

John Alverdy: Nice to see you.

Thank you.

Siobhan McCormack: We'll speak again sometime.

You take care.

Sounds good.

Bye now.

John Alverdy: Okay, bye-bye.

Intro and Outro: Thank you so much for listening to this episode of Microbiomedics Podcast.

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