[SPEAKER_00]: Hello and welcome to the Alcumian podcast.
[SPEAKER_00]: This is an exploration of woman kind.
[SPEAKER_00]: Here we discuss what it is to be a woman in the modern world while utilizing ancient and modern modalities in tandem to create a bounty of health for the body, mind and spirit.
[SPEAKER_00]: Good day everyone and welcome back to the pod.
[SPEAKER_00]: I hope you're having a beautiful morning afternoon, evening wherever you are in the world.
[SPEAKER_00]: Today we are talking all things UTIs, recurrent UTIs, the physiology behind them.
[SPEAKER_00]: And I guess like what you've been told about cranberry d-menos and
[SPEAKER_00]: wiping the right way and how that's only like 10% of the story and what the evidence actually shows, but before we get into it today, let's pay a respects to the oldest past, present and future residing in the lands of the chariota Tasmania where I'm recording this podcast today.
[SPEAKER_00]: Always has, always will be baby.
[SPEAKER_00]: More than half of women will have a UTI by the age of 32, so that's almost a third, we'll have another one, we'll be in six months.
[SPEAKER_00]: That's a few million billion women having UTIs.
[SPEAKER_00]: And the poll public conversation about how to stop that from happening is built around what your mother told you, what a cranberry marketing campaign told you, and what a supplement brand told you how convenient, and not surprisingly none of it is actually reflecting what the evidence actually says.
[SPEAKER_00]: In fact, in the last three, four years, the science around the prevention of UTIs,
[SPEAKER_00]: has been completely rearranged.
[SPEAKER_00]: The biggest best design trial of D Manos, yeah, that's supplement that you've been told to take.
[SPEAKER_00]: I told you to take, everyone found it does not work.
[SPEAKER_00]: Yeah, D Manos is fairly ineffective.
[SPEAKER_00]: In fact, instead, a drug most of us have never heard of called Methanamine Hippurate was shown to be as effective as a long-term antibiotic without any resistant problem.
[SPEAKER_00]: That is a huge, huge thing.
[SPEAKER_00]: A sublingual vaccine has recorded infection-free rates well over 50% and a very, very hyped injectable vaccine failed its phase 3 trial in February of last year and was pulled $250 million.
[SPEAKER_00]: did not work for a vaccine.
[SPEAKER_00]: And instead this sublingual vaccine has recorded infection free rates.
[SPEAKER_00]: So we're going to be talking about that as well.
[SPEAKER_00]: At the same time, the fundamental biology of what a UTI is and how it works has even changed.
[SPEAKER_00]: We now understand that your bladder is not sterile, it has a microdiabion.
[SPEAKER_00]: We've actually known that for over a decade, even though most doctors and health providers will tell you otherwise.
[SPEAKER_00]: I think a lot of people say, you're a 90 sterile, that is not the truth necessarily.
[SPEAKER_00]: your bladder and your even your ureda has a microbiome.
[SPEAKER_00]: E-coli, the bug behind 80% of UTIs does not just splash around in your bladder, it grips onto the wall using molecular hooks and burrows into the cells, and it builds hidden colonies inside of your tissue that any biotics can not always reach.
[SPEAKER_00]: So that explains the recurrence of some UTIs in some women.
[SPEAKER_00]: This episode, I hope, is going to give you the full picture.
[SPEAKER_00]: It's not a wellness formula.
[SPEAKER_00]: It's not a clinical show.
[SPEAKER_00]: We're just going to look at the whole science, the actual evidence, and we're also going to be looking at the hierarchy of that evidence and how we can basically sort of down.
[SPEAKER_00]: I'm going to explain it in a way that, of course, hopefully you understand really, really well, we're going to be sitting down.
[SPEAKER_00]: This is just a solo podcast, hopefully it goes for about an hour, sit down, go a few walk, grab your tea, settle in, let's talk all things UTIs.
[SPEAKER_00]: I'll show you how the evidence hierarchy before.
[SPEAKER_00]: This is how I'm going to be organizing it.
[SPEAKER_00]: So maybe you can come back to this at the start, if you're like, wait, what is middle tier again?
[SPEAKER_00]: So top tier, again, is that large, well-designed randomized control trial or meta-analysis?
[SPEAKER_00]: Mid tier is a mechanistically plausible, mixed or moderate evidence.
[SPEAKER_00]: Low tier is preliminary.
[SPEAKER_00]: So we're only just finding out the science, small or heavily anecdotal.
[SPEAKER_00]: A lot of what of kind of online wellness spaces will sell you is kind of that low tier, being marketed as top tier, D-Manos being a really good example of that.
[SPEAKER_00]: Actually, it's also one of mine who calls themselves a gut health expert who has no accredited training whatsoever.
[SPEAKER_00]: Talking about how D-Manos can treat a UTI which is incredibly problematic, incredibly problematic because that's not true and what we know about D-Manos is that it's pretty low tier evidence for treating or even preventing.
[SPEAKER_00]: a UTI.
[SPEAKER_00]: We have to remember as well.
[SPEAKER_00]: UTIs, you should be taking very, very seriously.
[SPEAKER_00]: I think a lot of women have them and because they're so common, we normalize dysfunction.
[SPEAKER_00]: And I think just because of the simple biology of our eurotar being fairly close to our anus and our rectal sphincter, that there is a bit of bacteria in this area that can creep upwards and we are as
[SPEAKER_00]: of our anatomy a little bit more susceptible to UTIs in comparison to men.
[SPEAKER_00]: So there's that kind of just physiology and why we're a little bit more susceptible to it.
[SPEAKER_00]: I think wiping the right way is something that women have been told, which is a really, really condescending.
[SPEAKER_00]: That's not necessarily what's going on a lot of the time, but that's just kind of what male doctors would say because of that reasoning of our anatomical function.
[SPEAKER_00]: But just because they are so prevalent and you might have them all the time, it does not mean they should be normalized and they should go untreated.
[SPEAKER_00]: I had a UTI so badly that I ended up in hospital.
[SPEAKER_00]: I'll tell you the story.
[SPEAKER_00]: I was working with Indigenous people and we were out on a camp.
[SPEAKER_00]: And I had my period and I was very in period underwear.
[SPEAKER_00]: For the first time and at this camp we didn't have a good place basically to wash and I did my absolute best.
[SPEAKER_00]: I was using lots of wet wipes.
[SPEAKER_00]: I was making sure I was wiping the right way, all of these things, but I was in the Northern Territory.
[SPEAKER_00]: It was hot.
[SPEAKER_00]: I had a really heavy bleed and I didn't have proper sanitation even though I really tried to keep myself clean and had kind of a wipe down if you know what I mean every single day.
[SPEAKER_00]: But when I flew home after this work trip, I got a UTI so bad.
[SPEAKER_00]: Back when this was happening, I had finished my degree, but I wasn't really looking to evidence as I do now and I wasn't looking to evidence hierarchy and I was just kind of following a few people online who I really believed.
[SPEAKER_00]: There were people online, like this gut health guy I was talking about for saying like cranberry juice, the amount of all of these things can treat you to you.
[SPEAKER_00]: And so I thought, okay, great.
[SPEAKER_00]: I have a little bit of a UTI hurts when I pee.
[SPEAKER_00]: So I'm just going to do what these people online are telling me to do.
[SPEAKER_00]: And one night I work up in the night with the most incredible pain of a felt in my life.
[SPEAKER_00]: Just in this huge heat in my back on one side of my back and just so much pain.
[SPEAKER_00]: Like I felt like I had a fire inside of me.
[SPEAKER_00]: from a year or two and I immediately knew that something was wrong, this is it three o'clock in the morning, and I just drove myself to the hospital.
[SPEAKER_00]: I presented and I was like, guys, something is really wrong.
[SPEAKER_00]: I think I have a really serious infection and of course it was a Saturday night and there were a bunch of people in there that they knew to prioritize in front of me.
[SPEAKER_00]: They just basically gave me some paracetamol and told me to wait, and I was writhing around in pain lying down on these plastic chairs, kept going up every 20 minutes,
[SPEAKER_00]: I'm in so much pain that just kept keeping paying killers and I was just like, okay, this is a nightmare.
[SPEAKER_00]: I feel like I'm going to die or I'm going to lose a kidney.
[SPEAKER_00]: I finally get in there and they take my labs and everyone's in the room immediately.
[SPEAKER_00]: They are talking about dialysis, they are talking about surgery, they are talking about all of these things.
[SPEAKER_00]: And thank
[SPEAKER_00]: In there, she was like, okay, wait as I can guys, let's just get her on some really strong antibiotics and antivirals and let's just put her on a drip.
[SPEAKER_00]: Let's just give her some really powerful painkillers and keep it on her within an hour.
[SPEAKER_00]: They came back and they said that they had been very surprised by my white blood cells, which is very concerning to here in an emergency room.
[SPEAKER_00]: The emergency doctors have been in the industry for a very, very long time.
[SPEAKER_00]: They're very experienced when they say that you should be very concerned.
[SPEAKER_00]: I was like, oh my god, I'm going to lose a kidney.
[SPEAKER_00]: I'm going to lose a kidney and they were like, your kidney is doing really badly.
[SPEAKER_00]: All of your markers are out.
[SPEAKER_00]: All this stuff.
[SPEAKER_00]: We're going to keep you overnight.
[SPEAKER_00]: And so I stayed there the night and I eventually got my, it's a miracle.
[SPEAKER_00]: They got my white blood cells down to a certain point and they kept me there for a while.
[SPEAKER_00]: And in the morning they were like, hey, you're looking really good.
[SPEAKER_00]: We're actually going to discharge you because they don't have any room in the actual hospital to take me in.
[SPEAKER_00]: and my labs miraculously turned around and they were like how close are you to the hospital and I said I'm literally five minutes away and they said cool okay we want you to present tomorrow we can do labs again and we're just going to keep you really close eye on you and I went home and just collapsed and I really couldn't get out of bed for about three days from this infection.
[SPEAKER_00]: That's an insane story.
[SPEAKER_00]: I want you to hear that.
[SPEAKER_00]: I had a UTI.
[SPEAKER_00]: I listened to people online and their chunky advice and I almost died.
[SPEAKER_00]: I almost lost a kidney.
[SPEAKER_00]: I almost lost a fucking kidney.
[SPEAKER_00]: If I lost the other one, I would have had to be on dialysis.
[SPEAKER_00]: So let this be your story.
[SPEAKER_00]: Please don't believe people online.
[SPEAKER_00]: This, this thing that happened to me radicalized me and I started to go, I need to start reading the evidence myself because I don't trust these fuckers online.
[SPEAKER_00]: And that's why I have these sentiments because I had it almost had a very, very serious life event.
[SPEAKER_00]: And I think you need to remember the reason why people don't die from UTIs is because of antibiotics.
[SPEAKER_00]: Okay.
[SPEAKER_00]: They are lifesaving medicine.
[SPEAKER_00]: There is a time to place for antibiotics.
[SPEAKER_00]: I know if you have recurring infections, you really don't want to take them.
[SPEAKER_00]: But if it gets to a point where you're starting to feel
[SPEAKER_00]: Backpain, you need to take antibiotics, you need to present your emergency doctor, you need to go to a doctor immediately.
[SPEAKER_00]: Okay, there are people dying in the West from UTIs because they refuse antibiotics.
[SPEAKER_00]: Are you about that life?
[SPEAKER_00]: You're going to die for someone online telling you that D-manels works when it doesn't.
[SPEAKER_00]: I hope not.
[SPEAKER_00]: So that's my story.
[SPEAKER_00]: Please listen to health providers.
[SPEAKER_00]: Please use antibiotics.
[SPEAKER_00]: I'm very pro antibiotics for this.
[SPEAKER_00]: I will just say that at the outset.
[SPEAKER_00]: When we're talking about UTIs, it's a lot about prevention.
[SPEAKER_00]: It's a lot about what's happening and why do women get more UTIs and how can we prevent that from happening?
[SPEAKER_00]: As I say, there is no prevention that you can do at home that isn't antibiotics.
[SPEAKER_00]: Okay, if you have a UTI and it's starting to get into that symptom where you're seeing the infection move up into your kidneys, take it seriously.
[SPEAKER_00]: Okay.
[SPEAKER_00]: So let's move on to the numbers and why this episode exists.
[SPEAKER_00]: So the epidemiology alone should convince you that we're not paying attention to this in the way that it really truly deserves.
[SPEAKER_00]: So women contract UTIs up to 30 times more frequently than men and we went and talked about the reason why previously.
[SPEAKER_00]: up to four and ten women who have a UTI will have another in within six months and recurrent.
[SPEAKER_00]: So this is the definition of what is a recurrent UTI is two plus in six months or three plus in twelve months, okay?
[SPEAKER_00]: And so that's a lot less than what I see women presenting in my clinic with.
[SPEAKER_00]: And that affects 20 to 30 percent of women who have had an initial infection.
[SPEAKER_00]: UTI is account for roughly 15 percent of all community anti biotic prescriptions.
[SPEAKER_00]: That's a lot.
[SPEAKER_00]: That's a lot of antibiotic prescriptions just for UTIs, and that number should make you sit up, right?
[SPEAKER_00]: One of the biggest of drivers of antibiotic use in women and therefore antibiotic resistance in women is a condition that we barely take seriously as a research priority.
[SPEAKER_00]: I was surprised, no.
[SPEAKER_00]: Are we shocked?
[SPEAKER_00]: Yes.
[SPEAKER_00]: So direct U.S. healthcare costs, it costs more than $3.5 billion a year.
[SPEAKER_00]: That's how much it costs in one country.
[SPEAKER_00]: for UTIs in women, indirect burden.
[SPEAKER_00]: So work last, broken sleep, sexual withdrawal, the psychological toll of never trusting your body and when it's about to flare up.
[SPEAKER_00]: And so where are we now?
[SPEAKER_00]: In 2026.
[SPEAKER_00]: So last year, the 2025 AUA CUA and SUFU guideline, update is the biggest re-ordering of the prevention evidence in over a decade.
[SPEAKER_00]: So we are working from that framework
[SPEAKER_00]: So the interventions that were previously fringe and really now recommended and some interventions are still being aggressively sold to do not actually make the evidence bar within this guideline.
[SPEAKER_00]: So that reordering is not filtering down to an average clinical care yet, but we're going to work through it.
[SPEAKER_00]: Hello, if you're health care provider and you're listening to this, welcome.
[SPEAKER_00]: Please go and find that.
[SPEAKER_00]: I'll just read it out again so you can find it.
[SPEAKER_00]: It's the 2025 AUA, C-U-A, and S-U-F-U guideline update on urinary tract infections.
[SPEAKER_00]: Just broadly, a lot of the data in that is on women because women over represent this infection, of course.
[SPEAKER_00]: So, how your urinary tract actually works?
[SPEAKER_00]: Let's talk about the physiology behind this so you can understand how a UTI can come about.
[SPEAKER_00]: So let's talk about your plumbing, right?
[SPEAKER_00]: So it's a one-way filtration and drainage system.
[SPEAKER_00]: You have two kidneys.
[SPEAKER_00]: They filter about 180 litres of plasma daily.
[SPEAKER_00]: Almost all of it is reabsorbed.
[SPEAKER_00]: And what is not reabsorbed is left and it is concentrated into one to two litres of urine.
[SPEAKER_00]: If you're
[SPEAKER_00]: They're a stagural, like me, you might be thinking, God, I'm more like the four to five.
[SPEAKER_00]: So, your eye drains through the urit is, so one from each kidney into the bladder.
[SPEAKER_00]: So, your bladder is basically this amazing muscle.
[SPEAKER_00]: It's a muscular reservoir, and on voiding, it will contract, and the sphinters in the public floor will relax, and urine will leave the urethra, and the opposite will happen when it is filling with your eye, which is basically plasma, from your entire body.
[SPEAKER_00]: So basically, Plasma is your blood, how your blood travels through your circulatory systems, all your veins, all of your blood vessels, goes through your heart.
[SPEAKER_00]: It's pretty amazing, actually.
[SPEAKER_00]: It goes to every single cell in your body, and that goes through the kidneys that filter it, and then that goes filters down through the rooters to your bladder, and then to your urethra, and it comes out.
[SPEAKER_00]: So again, that one way of filtration and drainage system in the body.
[SPEAKER_00]: So the defense system of this, the first one is the eurothelium.
[SPEAKER_00]: So the bladder is lined by a specialized epithelium called the eurothelium.
[SPEAKER_00]: The outer layer is an enormous flattened cells called umbrella cells, because they look like open umbrellas under a microscope.
[SPEAKER_00]: They're actually quite cute.
[SPEAKER_00]: They can live up to six months, which is pretty amazing, and they're armoured in three ways.
[SPEAKER_00]: So, one, they have tight junctions, just like the ones that we have in our colonocytes.
[SPEAKER_00]: In our gut, we have tight junctions that glue the cells together, so nothing leaks between them.
[SPEAKER_00]: We also have Europlacin plugs, and their crystalline protein plates that make up the surface almost impermeable.
[SPEAKER_00]: and the G-A-G layer gag.
[SPEAKER_00]: She's gagged.
[SPEAKER_00]: The gag layer, slippery, sulfated, sugar coating, and that makes bacteria struggle to grip on the inside of your bladder.
[SPEAKER_00]: There is a little bit of a horrible little irony here, evolution-respeaking.
[SPEAKER_00]: Europeans are coated in manners, sugars.
[SPEAKER_00]: a molecular hook that grabs onto manos.
[SPEAKER_00]: So the sugar inside of your oplac and plaques, that's that crystalline protein plate that makes it hard for bacteria to get past into us, past the bladder, is basically they have hooks onto the sugar that make up part of that structure, basically.
[SPEAKER_00]: Lock that in, okay, lock it in the back of your head right at down with your pen and paper.
[SPEAKER_00]: That explains why most interventions we discuss for the rest of the hour work or do not work, okay, because of the manners sugar inside of your euro plaque and plaques.
[SPEAKER_00]: Defense too, the flow, your own flow itself is defense, which is why, when people say, if you have a UTI, if you're on coming on, drink, drink, drink, drink, drink, drink lots of water, because flowing it out mechanistically will flush and physically wash his bacteria out before they
[SPEAKER_00]: urine also contains antimicrobial peptides and secretary IGA, and it also contains something called uro modulin.
[SPEAKER_00]: And that's a decoy that looks like a manosugar to eat coli.
[SPEAKER_00]: So basically traps fingers, ha ha, he's a fake manosugar that we're going to put in the urine.
[SPEAKER_00]: It
[SPEAKER_00]: grabs onto that and acts as a hostage tag in a way and they both leave the urine mechanistically.
[SPEAKER_00]: Your body evolved a d-coi for the exact hook that you call our users.
[SPEAKER_00]: How amazing is that?
[SPEAKER_00]: Defense 3, the female anatomy problem.
[SPEAKER_00]: So the predisposition is anatomical, not behavioral.
[SPEAKER_00]: So the female urethra is about four centimeters away from our rectum.
[SPEAKER_00]: and male urethra is about 20cm.
[SPEAKER_00]: The female urethra opening also sits close to the vagina and the anus, right?
[SPEAKER_00]: So a short commute from the gut-reversive wire to your sterile bladder.
[SPEAKER_00]: So this is not hygiene failing.
[SPEAKER_00]: It's just your anatomy, right?
[SPEAKER_00]: The framing that I think women with UTI get a lot of the time, it's because they're not cleaning up.
[SPEAKER_00]: You're not wiping the right way.
[SPEAKER_00]: You're not urinating face fast enough after sex.
[SPEAKER_00]: and that's done the real harm, right?
[SPEAKER_00]: So lots of behavioral blame here, decades of blame.
[SPEAKER_00]: On women who are fundamentally set up by their in anatomy, I think this is just a funny one, right?
[SPEAKER_00]: Unfortunately, this is what you get when we have male doctors who just don't know how to communicate sensitively and just don't know that this is just an evolutionary fallout that will impact women so negatively just by the set up of their anatomy.
[SPEAKER_00]: Basically what I'm trying to say, you don't get UTIs because you're dirty.
[SPEAKER_00]: You get them because you're your breath race four centimetres long.
[SPEAKER_00]: And it opens up into real estate crowded by two bacterial neighborhoods that like to colonise in a way and like to like to move around a lot.
[SPEAKER_00]: So you understand all of that wonderful.
[SPEAKER_00]: Let's move on to what a UTI actually is.
[SPEAKER_00]: So this is the taxonomy.
[SPEAKER_00]: So we have a symptomatic bacteria.
[SPEAKER_00]: We have bacteria in the urine, no symptoms.
[SPEAKER_00]: This is really common in older women, do not treat.
[SPEAKER_00]: So if we have a symptomatic bacteria turning up in a urine sample, and that woman is not showing any symptoms of a UTI, you do not treat, right?
[SPEAKER_00]: If an older woman is told her urine has bacteria in it, but you feel fine, that alone does not justify antibiotics, okay?
[SPEAKER_00]: I think that should be really rare.
[SPEAKER_00]: It's usually in pregnant women and older women when they do a urine sample sometimes their health provider will come back and say, you have a UTI, you need to take antibiotics.
[SPEAKER_00]: If you're asymptomatic, the guidelines I've read and the literature is suggests at present, suggests that you shouldn't be treated for that if you're asymptomatic.
[SPEAKER_00]: Maybe you could go, okay, interesting.
[SPEAKER_00]: I'm gonna take this antibiotic and I'm just gonna keep an eye on it and if I start to show symptoms, I will start taking it.
[SPEAKER_00]: Right?
[SPEAKER_00]: You could do that.
[SPEAKER_00]: That's an option for you.
[SPEAKER_00]: So that's kind of the first UTI.
[SPEAKER_00]: It is a urinary tract infection, but it's asymptomatic.
[SPEAKER_00]: So we don't treat it.
[SPEAKER_00]: Next we have cystitis.
[SPEAKER_00]: This is a bladder infection.
[SPEAKER_00]: So this is the burning, this is the constant urge,
[SPEAKER_00]: This is that aching above your pubic bone, sometimes visible in blood.
[SPEAKER_00]: So sometimes when you pee, you can see a little bit of blood.
[SPEAKER_00]: That's what we're going to spend most of this episode on.
[SPEAKER_00]: And then we have urethicis.
[SPEAKER_00]: So that's the urethar alone and it overlaps with several SDIs.
[SPEAKER_00]: So SDI scans might be a part of the workup.
[SPEAKER_00]: And then we have what I had.
[SPEAKER_00]: which is the infection of the kidney.
[SPEAKER_00]: This is serious.
[SPEAKER_00]: I had fever chills, flank pain, flank, is kind of your bat, nausea, vomiting, and it can progress to sepsis, which is basically your body is infected.
[SPEAKER_00]: That's so serious, please.
[SPEAKER_00]: Take that very, very serious.
[SPEAKER_00]: If you have burning,
[SPEAKER_00]: If you have fever, if you've one-sided lower back pain or both sides, that's not like a wait and see situation dull.
[SPEAKER_00]: That's not a wait and see diva, go to your GP, go to the ED.
[SPEAKER_00]: That's the single most important safety point of this episode.
[SPEAKER_00]: Don't do what I did.
[SPEAKER_00]: Don't be a dumb dumb like I was and listen to our souls on the internet.
[SPEAKER_00]: who have no credit and tools telling you what to do, who don't know how to read through the evidence, right?
[SPEAKER_00]: Okay, go to the ED, go to your GP.
[SPEAKER_00]: I think I've drilled that in.
[SPEAKER_00]: I think I have recurrent UTIs.
[SPEAKER_00]: So two plus and six months, three plus and 12 months.
[SPEAKER_00]: Once you cross that threshold, you need preventative strategies, not just to episode by episode treatment, and we were talking about how you can treat that, how you can prevent, and also how we can actually work on possible dysviosis in the system, chronic UTIs.
[SPEAKER_00]: So this is a pretty contested term.
[SPEAKER_00]: even recurrent for a little bit.
[SPEAKER_00]: Sometimes some people don't like it, but chronic UTI is really contested.
[SPEAKER_00]: This is persistent embedded infections that's standard cultures really miss.
[SPEAKER_00]: The science of this mechanism is really quite real, but treatment protocols are contested.
[SPEAKER_00]: So no one can make their mind up on this and we'll come back to this.
[SPEAKER_00]: So let's talk about Ecoli.
[SPEAKER_00]: So the reason why we're talking about Ecoli is because 80 to 90% of your community acquired uncomplicated UTIs are caused by this one strand, which is known as UPEC Ecoli.
[SPEAKER_00]: So ordinarily, Ecoli lives harmlessly in your gut,
[SPEAKER_00]: UPEC is a subtype that has evolved that specific toolkit for colonizing into your urinary tract.
[SPEAKER_00]: So what does that mean?
[SPEAKER_00]: The bug that gives you UTIs often comes from your gut microbiome.
[SPEAKER_00]: So using an evolutionary strategy to move from one niche microbiome, your gut, to another, your vagina, to another, your bladder and your kidneys and your ureta.
[SPEAKER_00]: So step one, the grip, UPEC,
[SPEAKER_00]: covers itself in like this hair-like filaments called Fembray or Pilar.
[SPEAKER_00]: The most important class is this type 1 Fembray, and the tip of that sits on a protein called Fem H, basically this fancy little hair.
[SPEAKER_00]: If I am H.
[SPEAKER_00]: That's the adhescent here.
[SPEAKER_00]: So FIM H is job is to bind two manos sugars.
[SPEAKER_00]: Okay, remember that hook we were talking about before.
[SPEAKER_00]: That's type one FIM Bray, FIM H, okay, little hook.
[SPEAKER_00]: So what's coded in manos sugars?
[SPEAKER_00]: That you're a plankton that is on our umbrellas cells, they can hook onto those.
[SPEAKER_00]: So step one of every single UTI, that Ecolay moves from your gut, from your colon basically, into your eurotar and into your bladder.
[SPEAKER_00]: And then that FIMH hook will grab the manos on that cell inside of your bladder, the ureplactin, and without the grip bacteria get flushed out with it, they are anchored against the flow.
[SPEAKER_00]: So they can hold on, imagine you're in a river, and you're a upec, and you're holding on to.
[SPEAKER_00]: a rock, right?
[SPEAKER_00]: You have these hooks.
[SPEAKER_00]: So this is also mechanism behind D manos.
[SPEAKER_00]: Flood the urine with free manos, so E coli will go wow, this is a party, I'm going to grab on to all of these instead of the bladder wall and it gets flushed out.
[SPEAKER_00]: It's a lovely theory and we'll get back to whether this holds up in trials later on.
[SPEAKER_00]: So step two is the invasion.
[SPEAKER_00]: So we are holding on with our hooks, the FIMH hooks, we're binding the triggers in the bladder and we're starting to internalize bacterium.
[SPEAKER_00]: The cell is starting to swallow the bacteria, right?
[SPEAKER_00]: So inside of the cytoplasm, so basically the plasma inside of the cell, E. coli replicates.
[SPEAKER_00]: So hooking on, getting into cell replication.
[SPEAKER_00]: So
[SPEAKER_00]: It's not replicating as bacteria.
[SPEAKER_00]: It's actually replicating as a really tightly packed structure.
[SPEAKER_00]: Thousands of bacteria clustered inside a single blood of cell.
[SPEAKER_00]: And it's shielded by your own cell wall because it's inside the cell, if you take an anti-microbial, right, an anti-bacterial supplement, an antibacterial medication, it's inside the cell.
[SPEAKER_00]: So it can't be treated, right?
[SPEAKER_00]: So this type of a coli that's inside of the cell is called an intracellular bacterial community, also known as an IBC.
[SPEAKER_00]: So,
[SPEAKER_00]: This was first described by Anderson at Al in Science in 2003.
[SPEAKER_00]: Its developmental pathway was then elaborated by Justice at Al in PNAS in 2004.
[SPEAKER_00]: So, if you want any of the resources for this, also remember all of the sources that I use to put together these podcasts are always accompanying.
[SPEAKER_00]: the accompanying article on this same subject, on my subject and Patreon so you can join via the links in this bio and you can get all of the sources so you can get all of these studies.
[SPEAKER_00]: What these guys found basically was a single bacterium can grow into an IVC of more of
[SPEAKER_00]: 10,000 organisms inside a singular cell, hidden from antibiotics, hidden from immune cells.
[SPEAKER_00]: Okay, so that's the recurrency that we're seeing here.
[SPEAKER_00]: It's a very smart little bacterium.
[SPEAKER_00]: Step three, the dormant reservoir.
[SPEAKER_00]: Okay, so not all the bacteria stay actively in the replicating pool.
[SPEAKER_00]: Some will drop into kind of this dormant state.
[SPEAKER_00]: This is called a quiescent intracellular
[SPEAKER_00]: they're sitting in the deeper layer of your bladder walls.
[SPEAKER_00]: They're not replicating fast enough for anti biotics to catch on.
[SPEAKER_00]: and the immune cells around this area are like everything looks normal because they're really smart and they keep in super quiet.
[SPEAKER_00]: They're hiding away.
[SPEAKER_00]: They can wake up weeks to months later and seed a brand new infection, right?
[SPEAKER_00]: And so this was worked out in 2006 by Maya Soakup and Hulk ran in PNAS.
[SPEAKER_00]: So this is the single best explanation for why women take an antibiotics.
[SPEAKER_00]: They feel better.
[SPEAKER_00]: and then they get another UTI six weeks later, okay, because the infection was never fully cleared.
[SPEAKER_00]: The short antibiotic use and that course cleared the actively replicating in extra cellular bacteria, so outside of the cell that we're causing the symptoms and the intracellular reservoir was sitting there the whole time, okay?
[SPEAKER_00]: So if your immune cells can't see it,
[SPEAKER_00]: your antibacterial and antimicrobial concert either, okay?
[SPEAKER_00]: So this is the biological reality, what of why neither wellness, nor mainstream medicine really can grapple with and understand specifically chronic UTIs that women have.
[SPEAKER_00]: If antibiotics and even things like D-manos, they cannot find intracellular reservoirs of E-coli.
[SPEAKER_00]: Okay?
[SPEAKER_00]: There is no medicine that encourages our immune cells to go and find out, become really good at detecting a coal-eye.
[SPEAKER_00]: This is a relationship that we've had with the coal-eye for such a long time.
[SPEAKER_00]: Modern science has only been around for about a hundred years, okay?
[SPEAKER_00]: Versus billions of years of evolution, okay?
[SPEAKER_00]: So that's where we're at and that's why
[SPEAKER_00]: I guess women have these chronic infections.
[SPEAKER_00]: It's because Ecoli is incredibly smart and our immune system can't fight them because they're really good at hiding out.
[SPEAKER_00]: Okay, what about the other pathogens?
[SPEAKER_00]: Okay, because they're about maybe four other ones that we generally see like staff is one of them, enter a caucus is one of them.
[SPEAKER_00]: It's generally the same broad logic with Ecoli.
[SPEAKER_00]: They grab on with a hook and they'd he's
[SPEAKER_00]: So with each of them, of course, they're all quite different, but they use the same mechanism, which I think is quite amazing and very, very smart of these little bacteria.
[SPEAKER_00]: So one of the biggest things that you've been told about your body is that your bladder is sterile because urine is sterile, not necessarily.
[SPEAKER_00]: So again, as I said previously, the bladder has its own microbiome.
[SPEAKER_00]: It's called the uro biome.
[SPEAKER_00]: And if you're interested, I spoke about this with
[SPEAKER_00]: of years ago, and I had her on the podcast to talk about her PhD in vaginal and penile microbiomes.
[SPEAKER_00]: And we also talked about the microbiome inside of our bloodout, the urobiom.
[SPEAKER_00]: So if you're wanting to learn a little bit more about the vaginal microbiome and how it plays into UTIs, that's a really great one to go and listen to as well.
[SPEAKER_00]: But the urobiom was recognized formally around 2010 to 2014.
[SPEAKER_00]: It took a really long time, so like four years, because standard urine culture was blind to it.
[SPEAKER_00]: So why a standard culture of urine misses the microbiome is really interesting.
[SPEAKER_00]: So that, generally, we take a very small volume of urine.
[SPEAKER_00]: So a tiny little cup, I think a few of us have done that.
[SPEAKER_00]: We incubate it for a short period of time, and we also use it and test it in a aerobic condition.
[SPEAKER_00]: So there's oxygen around.
[SPEAKER_00]: which doesn't really make any sense, because when we actually look at how we're testing, there isn't a small volume of urine.
[SPEAKER_00]: There is a large volume of urine.
[SPEAKER_00]: When we have our first here in the morning, it's about a whole cop.
[SPEAKER_00]: It's not incubating for a short period of time, right?
[SPEAKER_00]: Because our urine stays in our blood of our date hours, and it's not aerobic.
[SPEAKER_00]: It's anaerobic.
[SPEAKER_00]: So how we were testing our urine and testing for a microbiome,
[SPEAKER_00]: actually didn't make any sense, right?
[SPEAKER_00]: It's slow, it's fist disease.
[SPEAKER_00]: It's often an aerobic bacteria that make up your resident bladder community in your uro biomes.
[SPEAKER_00]: That's why took us a little bit longer because the context of how we were thinking about it didn't actually make sense when we look at the context of how our bladder actually is and how the uro biome actually exists in our body.
[SPEAKER_00]: So, what do these amazing scientists and researchers do?
[SPEAKER_00]: So they used 16 as ribosomal RNA gene sequencing, say that 10 times fast, and that identified bacteria by DNA signatures without needing to grow them.
[SPEAKER_00]: Super smart, my God, some of these scientists are so so smart.
[SPEAKER_00]: They also used
[SPEAKER_00]: uRine cultures EQUC.
[SPEAKER_00]: This is Wolf at Al in the Journal of Clinical Microbiology in 2014.
[SPEAKER_00]: So they use larger volumes of uRine, they use more media, they use varied atmosphere, and they also incubated for a lot longer, and therefore they were recovering organisms standard culture systematically misses, right?
[SPEAKER_00]: So they're like, how can we actually make up what the bladder actually looks like and how it actually exists in real time and will that bring up more different culture species basically if we take a huge bit of urine and we make sure it's anaerobic and it's an anaerobic environment and we keep it and we culture for a lot longer and we use different DNA sequencing what can we find and they found so much more in this area.
[SPEAKER_00]: Alongside this sampling really matters, so the Urethra and the vagina have their own dense microbial communities, paying into a cup actually covers and captures a lot of bacteria that whenever in your bladder, right?
[SPEAKER_00]: So sometimes some cervical mucus can come out and that can negatively impact how we test, right?
[SPEAKER_00]: So we can go, wow, there's a lot of lack of a solution.
[SPEAKER_00]: Chris Partis here, that doesn't make any sense, maybe it is there, maybe it's not, okay?
[SPEAKER_00]: And that's why the field is still so young, it's just really really hard to sample clearly also because we can't just put a swab in the urethra.
[SPEAKER_00]: That would really hurt, so that's why it's really really hard.
[SPEAKER_00]: and why this area of science is still developing.
[SPEAKER_00]: So what have we learned though?
[SPEAKER_00]: So in many women, the healthy bladder is dominated by lactobacillus species, particularly lactobacillus crospatus, right?
[SPEAKER_00]: And so I think for a long time scientists will like maybe that's just
[SPEAKER_00]: from the vaginal microbiome.
[SPEAKER_00]: But now we know it's probably from the bladder as well.
[SPEAKER_00]: So like to be serious, Chris Barters, we spoke about that in the podcast with Dr. Moira Bradfield, Strater.
[SPEAKER_00]: I talk about that a lot of my channel as well and my Instagram and stuff.
[SPEAKER_00]: Anyway, the same species that dominates that healthy vaginal microbiome has that same neighbor, right?
[SPEAKER_00]: So these lactobacillir, they produce lactic acid and anti-vacterial compounds that's keep all of the pathogens that could be in the bladder in check.
[SPEAKER_00]: So it's resistant to colonization, basically.
[SPEAKER_00]: It's too acidic so nothing can live there.
[SPEAKER_00]: So what happens when we have dysviosis, which is the loss of lactobacillus dominance, and we can also see the expansion of gardenerella, which is associated with bacterial
[SPEAKER_00]: and increase UTI susceptibility.
[SPEAKER_00]: So we have to note the word here are associated.
[SPEAKER_00]: Most of this evidence is still correlational, okay?
[SPEAKER_00]: Not causal.
[SPEAKER_00]: Correlation is this and this is correlated.
[SPEAKER_00]: Corsation is we know this causes this.
[SPEAKER_00]: We have not reached causation, okay?
[SPEAKER_00]: The paradigm we understand around this has shifted a lot, but the clinical evidence has not been fully built out yet.
[SPEAKER_00]: So keyword associated.
[SPEAKER_00]: And the caveat here that I think is really interested is the wellness industry has already raised ahead of the science here.
[SPEAKER_00]: So bladder probiotic products are being sold and the evidence base for most of these products.
[SPEAKER_00]: for women does not exist, okay?
[SPEAKER_00]: It does not exist.
[SPEAKER_00]: So if you're taking a bladder probiotic, maybe don't.
[SPEAKER_00]: Also because it's just the same as taking lactobacillus crispatus, okay?
[SPEAKER_00]: It's probably just a lot more extensive as well.
[SPEAKER_00]: Let's move on to why antibiotics are necessary but not sufficient, okay?
[SPEAKER_00]: If you have an UTI, you need antibiotics, full stop.
[SPEAKER_00]: Okay, do not treat an active UTI with cranberry juice, D-manos, oversy, apple cider vinegar, or any supplement that you saw a wellness influence of talking about it.
[SPEAKER_00]: Those are great for prevention, but if you have a UTI, if you have a symptomatic UTI, you need antibiotics.
[SPEAKER_00]: Okay?
[SPEAKER_00]: Right?
[SPEAKER_00]: All of these things that I said before, D Manos, Uber, ERC, Apple cider vinegar, wonderful, I think they're great.
[SPEAKER_00]: They will not work reliably, okay?
[SPEAKER_00]: If it descends into your kidneys while you experiment with these things, the consequences can be really, really, really severe.
[SPEAKER_00]: This is not a treat at home, okay?
[SPEAKER_00]: I said that before.
[SPEAKER_00]: So the first line agents for an uncomplicated society.
[SPEAKER_00]: So when you go to your pharmacy and Australia, they can do it over the counter after a small interview with your amazing pharmacists who have started for so long.
[SPEAKER_00]: And we love them.
[SPEAKER_00]: So the first one is Nutro Thurotonein.
[SPEAKER_00]: And so that is 100 milligrams twice a day for about five days.
[SPEAKER_00]: The next one is trimethoprim.
[SPEAKER_00]: So that's a 160 to 800 milligrams twice daily.
[SPEAKER_00]: For three days, if local resistance is under 20%.
[SPEAKER_00]: Then we have some other ones, like Foss for My Sim, that's a single three-gram dose, and then we have PIV-Messicillum, so that's a European first line for decades, more recently it's coming into the US.
[SPEAKER_00]: We usually in Australia, Tri-Methiprim is the one that you will see most likely.
[SPEAKER_00]: There are other ones too, like, as I prove focused in trying to pronounce these correctly, and beta-lactems.
[SPEAKER_00]: They're okay, like some of them are FDA-restricted for complicated societies, but the other ones that I said previously, their first line agents, and you should go with those.
[SPEAKER_00]: The paradox here, though, is that every single antibiotic course further depletes the commensal
[SPEAKER_00]: lactobacillus populations in your gut, your vagina, and in your bladder.
[SPEAKER_00]: So those are the exact populations providing colonization resistance and the intervention that clears the current infection of the coli most likely is actually creating the environment that makes the next one most likely.
[SPEAKER_00]: And so that's why in that 2025, a UA reordering of the evidence towards non antibiotic prevention matters so much.
[SPEAKER_00]: Like if you're actually looking to that guideline,
[SPEAKER_00]: big emphasis on how can we prevent these because we can't just keep slapping any biotics on this over and over and over again and then expect something different because then we are actually creating any biotic resistance.
[SPEAKER_00]: We're ruining the microbial communities here that prevent it in the first place.
[SPEAKER_00]: So that's what I really liked about that 2025 reordering of the evidence and that guideline around UTI's women.
[SPEAKER_00]: Okay, so let's get into the prevention
[SPEAKER_00]: well-designed RCTs or meta-analysis.
[SPEAKER_00]: Mitia is mechanistically plausible with mixed evidence.
[SPEAKER_00]: So we don't know, maybe we've just found this out, we're just building the evidence, or we thought this was really good, and we found out that it's not Latia, preliminary, small or heavily anecdotal, okay?
[SPEAKER_00]: Top tier vaginal estrogen.
[SPEAKER_00]: So I think a lot of women who are going through menopause, so peri and post-menopause women, this group of women are really, really highly associated with the development of UTIs.
[SPEAKER_00]: And one of the reasons why is because estrogen proliferates and supports the proliferation and colonization of lactobacillus crispatus in the bladder and in the vagina.
[SPEAKER_00]: Okay.
[SPEAKER_00]: So whenever we see dispiosis in the vagina, we also see it in the bladder for women who are peri and postmenopause, okay?
[SPEAKER_00]: So if you're peri or postmenopause or with recurrent UTIs and all vaginal dispiosis, please take this one thing from this episode.
[SPEAKER_00]: vaginal estrogen, please please please.
[SPEAKER_00]: please do it, please do it.
[SPEAKER_00]: Okay, don't believe all of that rubbish from years ago that it increases the risk of a breast cancer.
[SPEAKER_00]: I'm gonna do a whole episode on that, okay, trust me.
[SPEAKER_00]: I've got a few articles on my sub-strike and Patreon about how safe a hormone replacement therapy and specifically vaginal estrogen is, please, please, please.
[SPEAKER_00]: It's the single most effective non antibiotic prevention strategy available, okay?
[SPEAKER_00]: it's under prescribed at scale and that's really disturbing to me.
[SPEAKER_00]: So what's the mechanism here?
[SPEAKER_00]: Estrogen drops at menopause, pH in your vagina rises, which is not a good thing, okay?
[SPEAKER_00]: That's more alkaline.
[SPEAKER_00]: And that means that your reproductive age lactoseillide will deplete significantly.
[SPEAKER_00]: And that means that it's less acidic and we are more hospitable to dispyosis, so think more gardenerilla, think more candida, right?
[SPEAKER_00]: So this is why so many women who have never had a UTI in their entire lives start having them in their 50s, vaginal estrogen restores like to survive, okay, re-acidifies the vaginal pH, it restores the barrier,
[SPEAKER_00]: without significant systemic estrogen exposure.
[SPEAKER_00]: So if that's something you're worried about, even though I've just said that it's not something you should worry about that much, vaginal estrogen, please please please, it's really, really great.
[SPEAKER_00]: It's safe for the vast majority of women, including many with a history of breast cancer, if discussed appropriately, with your oncologist and with your gyna, okay?
[SPEAKER_00]: So, what's the evidence?
[SPEAKER_00]: Cochrane, review, and vaginal, non-oral estrogen, significantly reduces recurrence.
[SPEAKER_00]: 10 Kim at Al in 2023.
[SPEAKER_00]: They looked at 5,638 women.
[SPEAKER_00]: They looked at annual UTI frequency, and it dropped form from 3.9 to 1.8.
[SPEAKER_00]: after they started using vaginal estrogen.
[SPEAKER_00]: So that's about a 52% reduction.
[SPEAKER_00]: So if you were having six a year, you go down to three.
[SPEAKER_00]: If you were having three, you go down to one.
[SPEAKER_00]: That's pretty good, right?
[SPEAKER_00]: And when we look in the 2025 AUA guideline, the moderate recommendation is grade the evidence.
[SPEAKER_00]: So it's not A, but we know it's B, which is still pretty good.
[SPEAKER_00]: So, if your GP or Gino are hesitant, I would be surprised if they are, they shouldn't be if they've been reading the evidence, which is their job, print out the guideline and take it in.
[SPEAKER_00]: It is, without a doubt, the most underutilized evidence intervention in the whole UTI space.
[SPEAKER_00]: Okay?
[SPEAKER_00]: All right, next is Mathime and I Hyperrate.
[SPEAKER_00]: I'm going to spell that out so you can Google it because this girl I love her.
[SPEAKER_00]: She's a ghost girl.
[SPEAKER_00]: She's going to help you a lot.
[SPEAKER_00]: If you're thinking, I'm cycling.
[SPEAKER_00]: I don't really want to do vaginal estrogen.
[SPEAKER_00]: It might work for you.
[SPEAKER_00]: There is some evidence around that, but it's mostly for post and Perry menopause or women.
[SPEAKER_00]: This one is for you.
[SPEAKER_00]: So I'm going to spell it out ready.
[SPEAKER_00]: M-E-T-H-E-N-A-I-N-A.
[SPEAKER_00]: Next word, H-I-P-P-U-R-A-T-E-E-8.
[SPEAKER_00]: Because she does.
[SPEAKER_00]: So this is the drug most people, including G-P's.
[SPEAKER_00]: have never heard of.
[SPEAKER_00]: And now it's guideline endorsed as a first line option for recurrent UTIs.
[SPEAKER_00]: So how does it work?
[SPEAKER_00]: So it converts the maldehyde in acidic urine.
[SPEAKER_00]: So if a maldehyde acts as a non antibiotic urinary antiseptic, basically it kills bacteria in the urine directly.
[SPEAKER_00]: Not anywhere else.
[SPEAKER_00]: Okay.
[SPEAKER_00]: So it's not an antibiotic.
[SPEAKER_00]: It doesn't drive antibiotic resistance.
[SPEAKER_00]: It does not deplete your gut microbiome.
[SPEAKER_00]: So what's the evidence around here?
[SPEAKER_00]: So hardling at
[SPEAKER_00]: In BMJR of 2022, they looked at 240 women in the UK, and they used it.
[SPEAKER_00]: Right, they used 1 gram, twice daily versus a normal, prolactic antibiotic.
[SPEAKER_00]: So, asymptomatic UTI incidents, 1.38 per person per year, on Mathiam and I, versus 0.89 on antibiotics.
[SPEAKER_00]: Okay, not a huge difference.
[SPEAKER_00]: So, if you are wanting to take something that is a non-anibiotic, we know it can decrease symptomatic UTI incidents pretty significantly, okay?
[SPEAKER_00]: There is a differentiation with pre-specified and non-inferiority margins in that study, but whatever.
[SPEAKER_00]: So what is that translated?
[SPEAKER_00]: So a non antibiotic intervention performed approximately as well as daily antibiotics without the resistance or the dysbiosis costs.
[SPEAKER_00]: Okay?
[SPEAKER_00]: So if you are a woman on a long-term antibiotic for recurring UTIs,
[SPEAKER_00]: what happens?
[SPEAKER_00]: I would love to see a longitudinal study in this like three, four years.
[SPEAKER_00]: That would be great because we would actually see are these women who are on the antibiotic?
[SPEAKER_00]: Are they taking it more often?
[SPEAKER_00]: And are we starting to see gut and vaginal dysviosis?
[SPEAKER_00]: So is there some negative outcome with this medication?
[SPEAKER_00]: First is what happens with the women who are taking this non-anibariotic
[SPEAKER_00]: do we see that they have less incidents of vaginal and gut and also your bladder dysviosis and we're also seeing a decrease in UTIs.
[SPEAKER_00]: I think that would be really fascinating, but more on this space, it's coming.
[SPEAKER_00]: The next one, drum roll, surprisingly high up in this guideline, increased water intake.
[SPEAKER_00]: It sounds obvious, but the trial data on it is really strong.
[SPEAKER_00]: So Hutan et al in jamma internal medicine in 2018, they looked at 140 premenopoles of women
[SPEAKER_00]: and they randomized to an additional 1.5 liters a day or usual in tech.
[SPEAKER_00]: So their two groups, one was not drinking that much water, the yellow with the other one was drinking more water.
[SPEAKER_00]: So over 12 months, the mean cystitis episode fell from 3.2 to 1.7.
[SPEAKER_00]: Mean antibiotic courses fell from 3.6 to 1.9.
[SPEAKER_00]: We are seeing the geese women literally drinking just double the amount of water so from 1.5 liters to 3 liters.
[SPEAKER_00]: They saw the cystitis go down by half and they're antibiotic courses falling down by half as well.
[SPEAKER_00]: Drink your water gals.
[SPEAKER_00]: Please drink your water.
[SPEAKER_00]: So the time between infections also stretched as well.
[SPEAKER_00]: From 84 days to 143 days.
[SPEAKER_00]: So the caveat here though, the effect was low in low volume drinkers specifically.
[SPEAKER_00]: So piling more water on to already adequate intake.
[SPEAKER_00]: is not showing any benefit.
[SPEAKER_00]: It's just if you're a low water drinker if you don't drink a lot of water in the day you can really make a huge difference by drinking more water.
[SPEAKER_00]: I'm so sorry it's so obvious but I had to point it out because the evidence is really interesting and obvious at least to me.
[SPEAKER_00]: The next is cranberry, you knew it was coming, so there's a huge image problem here, okay?
[SPEAKER_00]: So it sounds like folk medicine and it's marketed by juice companies for decades, and this is our gear back and forth in the literature, but when we look into the literature, so 2023, co-crain review by Williams at how they looked at 50 randomized control trials that included 8,857 participants.
[SPEAKER_00]: So, this is a huge study.
[SPEAKER_00]: The relative risk for symptomatic culture identified as 0.7 overall and 0.74 in recurrent UTIs.
[SPEAKER_00]: Okay, so the mechanism behind this is that A-type antibiotic PACs, they inhibit binding of p-fimbre, which is a second E-colay adhesive to the receptors.
[SPEAKER_00]: Okay, so basically, cranberry can stop the hook from working, one of the other hooks from working inside the bladder.
[SPEAKER_00]: There's lots of caveats around cranberry juice though, okay?
[SPEAKER_00]: Product quality varies really quite enormously.
[SPEAKER_00]: PAC content is often not disclosed on the packaging.
[SPEAKER_00]: Right, so PAC is the kind of the one we want to look for.
[SPEAKER_00]: PACs are in the cranberry juice, and they stop that hook from working.
[SPEAKER_00]: A supermarket cranberry juice cocktail is mostly sugar.
[SPEAKER_00]: It does not deliver any therapeutic PAC dose.
[SPEAKER_00]: And if you use instead a standardized extract with disclose PAC content, you're going to be a lot better off.
[SPEAKER_00]: And again, this is not treatment, this is prevention.
[SPEAKER_00]: Okay, so those were all of our top tier.
[SPEAKER_00]: Let's move on to our mid tier.
[SPEAKER_00]: First one is probiotics.
[SPEAKER_00]: So really compelling when we look at the mechanistic rationale, but when we look into the clinical data, it's pretty mixed.
[SPEAKER_00]: So the mechanism here, if we restore the protective vaginal and gut-lact specialist populations, that's going to positively impact the bladder, right?
[SPEAKER_00]: So in a staple turn at alphabets,
[SPEAKER_00]: study, basically they call it the Lactin V trial.
[SPEAKER_00]: They use vaginal lactobacillus crispatus.
[SPEAKER_00]: So when they reduced lactobacillus crispatus or they saw a reduction in vaginal lactobacillus crispatus in women, it did not reach a statistical significant overall.
[SPEAKER_00]: So they didn't see a change in UTIs in women.
[SPEAKER_00]: But there was a strong dose-dependent response in the women who were successfully colonized.
[SPEAKER_00]: So basically, when we take healthy women and we see a reduction in their vaginal lactobacillus, we didn't see any change in their UTIs.
[SPEAKER_00]: But if we took women with low lactobacillus and we brought it up, we did see a reduction in UTIs in that group.
[SPEAKER_00]: which is pretty interesting and so that's why it's mid-tier because it's a bit mixed.
[SPEAKER_00]: A different study, so Gupta et al in 2024, combined oral and vaginal probiotics, reduced via currents rate of UTIs, so lactobacillus crisp body, putting it in your vaginal microbiome, so you're putting it as a pestering inside of your vaginal canal, and you're also taking it early, we saw a reduction, that's cool.
[SPEAKER_00]: So strain, dose and delivery route all really matter a lot,
[SPEAKER_00]: and consumer products really match the specific formulations used in these trials, okay?
[SPEAKER_00]: So, if you are like, okay, that sounds great.
[SPEAKER_00]: I want to try and do an oral and vaginal.
[SPEAKER_00]: You want to look for the lack of a syllabus for spartars, lack of a syllabus, remnoces, GR1,
[SPEAKER_00]: may be lacked bestsellers, rotary RC14, okay?
[SPEAKER_00]: Those are the ones that we see in trial doses, ideally from a company disclosing the strain level detail as well.
[SPEAKER_00]: Next up we have post-quietal antibiotics.
[SPEAKER_00]: Yes, antibiotics that you take specifically after you have sex.
[SPEAKER_00]: So they're trying to be effective.
[SPEAKER_00]: But they're in mid tier because the mechanism is an antibiotic and we know with this also comes resistance and dysviosis and those costs still apply.
[SPEAKER_00]: So for a woman who consistently gets a UTI after sex, a single dose of targeted antibiotic within a couple of hours of intercourse,
[SPEAKER_00]: can really dramatically reduce the reoccurrence of that UTI.
[SPEAKER_00]: But again, the risks associated with the depletion in your microbiome in your bladder are significant and it's not associated with a you know, a kind of a, and it's supported microbiome there that's going to naturally decrease the reoccurrence.
[SPEAKER_00]: It's mid-tier because there's risk.
[SPEAKER_00]: Lotia.
[SPEAKER_00]: Okay, let's get it to you straight.
[SPEAKER_00]: I've been asked this a thousand times previously the D-Manosphere.
[SPEAKER_00]: It was like, wow, this is amazing.
[SPEAKER_00]: And I recommended this and I've used this and I think it has been effective anecdotally for me.
[SPEAKER_00]: I think, but the more you look into the evidence now, after the huge trials have been done, the wellness industry has not caught up with this.
[SPEAKER_00]: Okay, there are still people online saying that D-Manos is the best thing.
[SPEAKER_00]: since cut bread for UTIs and it's just not true.
[SPEAKER_00]: The mechanism is still beautiful, okay, and I love that for her.
[SPEAKER_00]: So, free Manos Sugar competitively binds for the Finn Hage adhesion.
[SPEAKER_00]: Remember that hook?
[SPEAKER_00]: That's on Ecoli.
[SPEAKER_00]: So it's like a big Manos Sugar party.
[SPEAKER_00]: Here's all the sugar in the world.
[SPEAKER_00]: Ecoli goes, whoa, whoa, whoa, whoa.
[SPEAKER_00]: hooks on and then is mechanistically taken out with your right flow.
[SPEAKER_00]: Okay, so that's really the kind of intervention that should work.
[SPEAKER_00]: When we looked into early trials, so in crangec in 2014, this was an open label study.
[SPEAKER_00]: It was really promising.
[SPEAKER_00]: and this enthusiasm around the manos really built and then from that singular study which was I guess it was a primary study.
[SPEAKER_00]: A lot of people were really excited and products really started to flood the market and then the definitive trial which is in Merit so hey would it al jama International Medicine 2024 it's called Merit.
[SPEAKER_00]: are they looked at 598 women in UK?
[SPEAKER_00]: They took two grounds a day of D Manus versus a placebo, double blind for six months.
[SPEAKER_00]: The result was clinically suspected UTI in 51% of D Manus versus 56% of placebo.
[SPEAKER_00]: That's not good.
[SPEAKER_00]: That shows no benefit.
[SPEAKER_00]: There's only a 5% reduction in D Manus.
[SPEAKER_00]: Okay, the authors, this is a near direct quote.
[SPEAKER_00]: D-manos should not be recommended to prevent future UTIs in women with recurrent UTIs in primary care.
[SPEAKER_00]: And then we've also seen subsequent meta-analysis confirm the port of fact that is not statistically significant.
[SPEAKER_00]: So a bit awkward, a bit awkward for the gut experts online isn't it?
[SPEAKER_00]: Does this mean that D-manos does nothing for any woman ever?
[SPEAKER_00]: No!
[SPEAKER_00]: Okay, individual responses real.
[SPEAKER_00]: I just spoke about it.
[SPEAKER_00]: If it works for you, I'm not there to tell you to stop.
[SPEAKER_00]: I'm just saying that don't choose D Manos over any of the top tier events that just spoke about.
[SPEAKER_00]: Okay, I would rather see a woman on vaginal estrogen or methiamenion Hippurate, then on D Manos.
[SPEAKER_00]: if she was choosing between them, okay?
[SPEAKER_00]: Lastly, let's talk about behavioral interventions and myth-busting, so this is counter-intuitive.
[SPEAKER_00]: The behavioral interventions that dominate the public conversation and also the private conversation between you and your doctor is whapping direction.
[SPEAKER_00]: If you're narrating after sex, don't go in hot tubs, don't go and where heeps a tight underwear, don't do she ever gyna, which I don't think you should do, you have a gyna anyway, I digress.
[SPEAKER_00]: So these have all been examined individually and also some of them collectively.
[SPEAKER_00]: In case control studies and they'd be also been incorporated into that 2025 AUA guideline.
[SPEAKER_00]: They did not meaningfully reduce rear currents.
[SPEAKER_00]: This does not mean stop doing them, okay?
[SPEAKER_00]: Wiping front to back is not going to harm you, statistically speaking, but if you are already doing all of that faithfully and still getting infections, do not spend another minute of your life blaming yourself and sitting there and watching your doctor try and blame you.
[SPEAKER_00]: Okay, so to behave your interventions exist with real evidence, increased fluid intake in low volume drinkers that we spoke about previously, and discontinuing your spermicide and diaphragm contraception.
[SPEAKER_00]: So if you have UTIs and you're using spermicide,
[SPEAKER_00]: or diaphragm, both of those really seriously disrupt the protective, vaginal lactobacillus crispatus.
[SPEAKER_00]: And if you use those and you have recurrent UTIs, if you just change your contraceptive method a little bit and you see improvement, that's actually one of the highest yields interventions that we have behaviorally as well.
[SPEAKER_00]: Next let's talk about the vaccine frontier.
[SPEAKER_00]: It's all very exciting.
[SPEAKER_00]: And so UTI vaccines are real.
[SPEAKER_00]: One is now available in about 26 countries.
[SPEAKER_00]: Results are frankly really extraordinary compared to any supplement that we've spoken about here.
[SPEAKER_00]: So...
[SPEAKER_00]: What am I talking about?
[SPEAKER_00]: I'm talking about MV 140 or so known as Euromune.
[SPEAKER_00]: It is a sub-lingual spray, so you just spray it under your tongue daily for three months.
[SPEAKER_00]: Yes, that's all it is.
[SPEAKER_00]: That's a vaccine.
[SPEAKER_00]: How wonderful is that?
[SPEAKER_00]: So it contains wholesale in activated preparations in the foremost common European pathogens.
[SPEAKER_00]: So using that sub-lingual route induces mucosal and t-cell immunity.
[SPEAKER_00]: Okay, and you can find all of this out from the pivotal trial.
[SPEAKER_00]: in NEJM evidence of 2022.
[SPEAKER_00]: So this is a double-blind RCT that used 240 women and this was done in Spain and the UK.
[SPEAKER_00]: So three months of dosing produced infection-free rates of 56% of the women at three months and 58% at nine months versus 25% for the placebo which took none.
[SPEAKER_00]: Medium number of infections fell from three to zero so most of these women were experiencing
[SPEAKER_00]: and it fell down to zero, and the medium time for first infection went from 48 days to 275 days.
[SPEAKER_00]: Wow!
[SPEAKER_00]: Okay, so that's really crazy, right?
[SPEAKER_00]: High-quality data from a properly designed unanimous control trial.
[SPEAKER_00]: Okay, that's the reason why MV 140 is now available in 26 countries, including Australia.
[SPEAKER_00]: by a pain-named patient access, okay?
[SPEAKER_00]: So if you have recurrent UCIs and you have not found relief from top tier prevention strategies, MV 140 is really, really, really worth talking to your GP, yourologist, your gynecologist about, right?
[SPEAKER_00]: Further RCTs are underway, including one in Australia, which is really, really exciting.
[SPEAKER_00]: Okay, so that's the sub-glint-lingual vaccine, really, really cool.
[SPEAKER_00]: What about the other one that we heard about, right?
[SPEAKER_00]: So the EX-PEC,
[SPEAKER_00]: 9V failure.
[SPEAKER_00]: So the context here really matters.
[SPEAKER_00]: Let's talk about it.
[SPEAKER_00]: So in February 2025, a very, very large, very, very, very expensive phase 3 trial failed.
[SPEAKER_00]: So XPEG 9V by Jassen and San Furi.
[SPEAKER_00]: This is an injectable 9valent conjunctant vaccine.
[SPEAKER_00]: So it's designed to prevent invasive E coli disease by including bloodstream infection in older adults with a UTI history.
[SPEAKER_00]: So the E dot brace, so the M brace trial halted really early, um, independent data monitoring committee showed that it was not sufficiently effective compared to the placebo.
[SPEAKER_00]: So since Ophi took a $250 million charge on the program, that's really sad, isn't it?
[SPEAKER_00]: So basically what I'm saying is mechanistically this looked perfect, but it did not guarantee clinical effectiveness.
[SPEAKER_00]: So they showed that the placebo was doing as good as the vaccine.
[SPEAKER_00]: So they said this trial is over because it's not showing benefit.
[SPEAKER_00]: Therefore, you can cause harm to the people who in this trial.
[SPEAKER_00]: So that's why I closed.
[SPEAKER_00]: Okay, let's talk about chronic UTIs and the ecosystem view.
[SPEAKER_00]: So I think we've touched on this a little bit.
[SPEAKER_00]: So recurrent and chronic UTIs are not really a single bladder problem.
[SPEAKER_00]: It's an ecosystem across three connected niches.
[SPEAKER_00]: So niche one is the gut.
[SPEAKER_00]: So this is the primary reservoir for E coli, whether bacteria that end up in your bladder actually,
[SPEAKER_00]: live.
[SPEAKER_00]: So in Warby at Al in the Nature Microbiology in 2022, women with these recurrent UTIs have distinct gut microbiome profiles.
[SPEAKER_00]: So generally, generally, they will have reduced diversity and expanded Ecoli populations.
[SPEAKER_00]: Okay, so if you have a gut like that, you're a lot more likely to have a vaginal dyspiosis problem and a bladder dyspiosis problem.
[SPEAKER_00]: So gut Ecoli abundance rises
[SPEAKER_00]: Antibiotic treatment.
[SPEAKER_00]: So that's why if you're in Bali and you've got Bali belly and you took it antibiotic and then you have a UTI, it's because
[SPEAKER_00]: After two weeks of taking that, he called I can rise, and so that's why we generally see that association between antibiotics and the development of UTIs, because E. coli is like great.
[SPEAKER_00]: All of these really beneficial microbes are out of the way.
[SPEAKER_00]: They've been wiped out, so I can be opportunistic, and I can grow and colonize.
[SPEAKER_00]: Nish 2 is the vagina, so this provides either colonization resistance through
[SPEAKER_00]: for uropathenogen ascension when lactobacillus is depleted.
[SPEAKER_00]: So, how does lactobacillus get depleted?
[SPEAKER_00]: Menopause, because we don't have any estrogen antibiotics.
[SPEAKER_00]: Work, we just spoke about before, spermicides, and some hormonal contraceptives can drop lactobacillus as well.
[SPEAKER_00]: So once vaginal microbiomes shift the European pathogens like a coli have somewhere to establish before the short climb up to the urethra.
[SPEAKER_00]: Nish 3 is the blood of wool.
[SPEAKER_00]: Okay, that's where the IVCs and the QIRs live and that's why symptoms come back six weeks and then six weeks and then six weeks.
[SPEAKER_00]: after clean courses of antibiotics, okay, because the infection has never fully cleared.
[SPEAKER_00]: It was suppressed enough that you were asymptomatic, but the reservoir of the coli and other pathogens is still there.
[SPEAKER_00]: And so we uncovered this really vicious cycle, right?
[SPEAKER_00]: So each antibiotic course clears the current infection, but the cost is large, right?
[SPEAKER_00]: It depletes the commensual populations providing colonization resistance, so lactobacillus, criss-partis, mostly.
[SPEAKER_00]: creating an acidic environment.
[SPEAKER_00]: It increases the risk of the next infections and that next infection will need more antibiotics and then that further depletes the microbiome and so on and so on.
[SPEAKER_00]: And also inside of this is that massive problem of antibiotic resistance.
[SPEAKER_00]: Okay, every time we use antibiotics, the risk of antibiotic resistance can increase.
[SPEAKER_00]: let's talk about the chronic UTI controversy.
[SPEAKER_00]: Okay, so let's address this just because I know a few of you are dealing with symptoms that fall between the cracks.
[SPEAKER_00]: So your culture comes back negative your T.P.
[SPEAKER_00]: tells you it's all in your head.
[SPEAKER_00]: have been given antidepressants when you know that something is really wrong.
[SPEAKER_00]: So what's going on here?
[SPEAKER_00]: That's the underlying science of embedded intracellular infection and that's a legitimate okay.
[SPEAKER_00]: So IBCs and QIRs are real.
[SPEAKER_00]: And standard urine culture does miss these persistent infections particularly ones dominated by bacteria.
[SPEAKER_00]: that do not grow well under other standard conditions, okay?
[SPEAKER_00]: So that's a really genuine and unmet need.
[SPEAKER_00]: Women reporting these symptoms are not making it up.
[SPEAKER_00]: If you're a health provider and you're listening to this, and you're like, oh my god, why do I have so many menopoles of women coming to me saying that they have UTIs when they don't?
[SPEAKER_00]: You should fucking listen to them, consider listening to women.
[SPEAKER_00]: Did you know that there's like 40 grams of protein in listening to women?
[SPEAKER_00]: I digress.
[SPEAKER_00]: So the specific long course antibiotic protocols used by some chronic UTI clinics months to over a year of continuous antibiotic exposure sounds super good in healthy.
[SPEAKER_00]: Rest on observational and patient reported data, not RCTs.
[SPEAKER_00]: That's a real risk.
[SPEAKER_00]: Okay, real risk number one antibiotic resistant risk to gut dispayosis.
[SPEAKER_00]: Those have longer to do your negative health impacts over the lifespan.
[SPEAKER_00]: But I think when you present to someone and you say I have an infection, I think health providers
[SPEAKER_00]: UTIs are so serious and they can cure this person so we just need to wipe it out.
[SPEAKER_00]: And I understand that, but there also needs to be a conversation around, I've seen you six times in the post-Gia.
[SPEAKER_00]: This is really concerning how can we prevent this from happening in the future, but health providers just haven't read through the literature to know about how to prevent this in the future.
[SPEAKER_00]: Right?
[SPEAKER_00]: So chronic UTI as a diagnosis is at a genuine risk of being over applied.
[SPEAKER_00]: Sometimes it displaces other diagnoses like interstitial cystitis or pelvic floor dysfunction that also need treatment entirely and also can
[SPEAKER_00]: co-exist with this.
[SPEAKER_00]: So let's talk about public floor baby.
[SPEAKER_00]: Okay, this is the last piece before we close up the pelvic floor I also have a podcast all about the pelvic floor with the amazing pelvic floor pt That that we did in my gorgeous lounge room Okay, Emma, so she's amazing go and listen to that So basically if the bladder does not empty completely Residual urine becomes a pool and this great playground where bacteria multiply between voids and by void I mean
[SPEAKER_00]: each P. So mechanistically, this is a really obvious risk factor for recurrent UTIs, and it's actually one of the most under-investigated pieces of the puzzle in ordinary practice.
[SPEAKER_00]: So, what are some of the causes of incomplete emptying?
[SPEAKER_00]: So, pelvic floor dysfunction or dysfunctional warding?
[SPEAKER_00]: This is where your pelvic floor and your urinary sphincter, they fail to relax during urination, so interrupted or sackedo stream, so that's basically where you're not knowing when to stop, and so you might stop early, or you might pee and stop and pee and stop.
[SPEAKER_00]: That's not normal, you should just pee and then you stop, and there shouldn't be much left.
[SPEAKER_00]: Another one is pelvic organ prolapse, so anatomical decent kinks in the urethra,
[SPEAKER_00]: like a bent hose, basically.
[SPEAKER_00]: You can't actually fully release all of your urine.
[SPEAKER_00]: And there might also be that bladder muscle does not generate enough contraction to empty fully.
[SPEAKER_00]: So residual urine sits in the bladder itself, not the uritis.
[SPEAKER_00]: That's actually something I've seen in wellness circles a lot.
[SPEAKER_00]: And it's like, no, doesn't work that way.
[SPEAKER_00]: Gravity will help it fall out.
[SPEAKER_00]: Maybe if you have a really big hink because of pro pelvic organ prolapse, that might be the case.
[SPEAKER_00]: But
[SPEAKER_00]: very often that's not what can happen is when your bladder pressures rise or the flat valve where the urit is meet the bladder fails the urine refluxes backwards and up into the urit is towards the kidneys.
[SPEAKER_00]: So that is called VUR and that mechanism is by which you incomplete empty and can predispose not just two infections and lower tract infections so
[SPEAKER_00]: So the chain here basically I want you to understand.
[SPEAKER_00]: In complete emptying, you run pooling in the bladder, bacteria or overgrowth, and potentially reflux into the urit is in the kidneys that can lead to kidney infections as well.
[SPEAKER_00]: So what to do?
[SPEAKER_00]: If you have recurrent UTIs and you have an interrupted urine stream, if you don't feel like your bladder has fully emptied after urinating, if you need to go shortly after you've peed, those are symptoms of maybe some problems there.
[SPEAKER_00]: If you also have symptoms of pelvic organ prolapse,
[SPEAKER_00]: What do you do?
[SPEAKER_00]: Go to a public floor physiotherapist, they're going to do a few exercises with you, and they'll assess whether if you're overactive or underactive and what's going on and give you some exercises to do as well.
[SPEAKER_00]: You can also ask your GP or your urologist for a post-void residual measurement, which is basically a really simple measurement, an ultrasound where you go have a P and you come back and they see if there's still some
[SPEAKER_00]: in your bladder, right?
[SPEAKER_00]: And then if you find any of those things a true, you can do some pelvic floor physiotherapy, and I've actually seen that be very, very successful for women if you can fully let go of all of your pee.
[SPEAKER_00]: you're basically not allowing and a good environment for a coli to overgrow.
[SPEAKER_00]: Hopefully you enjoyed this podcast.
[SPEAKER_00]: Okay, I think I covered absolutely everything I needed to with UTI and I'm going to get a bunch of comments below.
[SPEAKER_00]: What about this?
[SPEAKER_00]: What about that?
[SPEAKER_00]: What about this supplement go and look at the guideline, go and read the sub-stack, go and read the Patreon article on this as well.
[SPEAKER_00]: You can access all of the references
[SPEAKER_00]: in APA.
[SPEAKER_00]: We love that.
[SPEAKER_00]: I will see you on the next one.
[SPEAKER_00]: Thank you so much for taking the time out of your busy day to listen to this episode.
[SPEAKER_00]: If you loved it, please remember to like, subscribe, and send to a loved one.
[SPEAKER_00]: If you want to learn more from our quaman, please check out the website at arquaman.com.au, where you can find a
[SPEAKER_00]: or sub-stack.com slash our comment to join the community.
[SPEAKER_00]: I hope you have a really beautiful morning, afternoon or evening wherever you are in the world, and I will see you on the next episode.