In this series of 3 podcasts, we'll be discussing the complex world of the microbiome, the diseases and disorders that can occur when it's disrupted. What the emerging research is saying and what practitioners can do to re-establish a healthy bacterial balance for their patients. This series is sponsored by Protecting Veterinary and is in partnership with the British Veterinary Association.
In this episode of the podcast, we look at the microbiome in relation to kidney disease. We'll discuss the normal microbiome of the urine and what happens when that is disrupted. The diagnostic and treatment options for conditions arising from urinary dysbiosis, particularly whether dietary therapy is useful, how the gut biome may may affect the kidneys, and finally, we'll look at where research on the microbiome and its associations with kidney disease may be headed in the future.
We're joined today by Emily Coffey, Assistant Professor of Internal Medicine in the Veterinary Clinical Sciences department at the University of Minnesota. Emily's clinical and research interests include infectious diseases, microbiome science, host microbiome interactions, urinary tract infections. Faecal micro butter transplants and antimicrobial stewardship.
So welcome, Emily and thanks for joining us. Yeah, thank you so much for having me. It's great.
Certainly a lot of interesting clinical research areas there, so I think you'll definitely be able to help inform us on this particular. The topic. So I suppose from your point of view, perhaps the first, if you could just set out for us what a normal urinary microbiome looks like and, perhaps how it differs from the gut biome.
So, so that is a great question. It's probably one of the ones I get asked more than anything else. And, I'll preface all of this by saying, This field is very much in its infancy and so I'll probably be a little bit annoying today where there's a lot of things where I say I'm not sure, we need more data, .
But with, with what the urinary microbiome actually looks like, we, we actually do, we're starting to assimilate more and more data about that, at least in dogs, we're still quite limited in cats and in people, they're they're quite a ways ahead of us. So, What we're observing is that just like in other anatomic sites, the urinary microbiome seems to have a very broad range of what's considered normal, and so that can really shift with all kinds of factors, so things related. To age and sex and breed and external variables, environmental variables, things like that.
So we know that in the majority of studies looking at the urinary microbiome in dogs, there's dominant phyla, so proteobacteria and fermacues are typically the most dominant phyla with actinob bacteriota kind of shortly behind. That's very, if you remember your taxonomic levels, the phyla are pretty high up, so that's kind of a broad umbrella. But when you look in more closely, some of the, some of the big players in the urinary microbiome are ones that we're already familiar with as clinicians, so we tend to see strep staph, carin bacterium, Echo, Pseudomonas, Ainidobacter.
So bacteria that we've all heard of, we also see a lot of kind of strange bacteria that we, we probably aren't as familiar with. So that's sort of a long-winded way of saying we, we think there's a lot of different things that can be considered normal in the urine based on what we're seeing. There.
It is a pretty distinct shift between the urine and the gut microbiota. We know there is probably some overlap and some crosstalk between the two, but, for instance, the very first study that came out looking at the urinary microbiome in dogs back in 2017, Looked also it compared it directly to rectal swabs from the same dogs and, and there were some pretty distinct differences. So, I suspect there's crosstalk, but there are also very unique populations in their own right.
And is that due to I suppose the more sort of sterile nature, do you think of? The the urinary tract system in in comparison to the gut or is there something else going on there? Yeah, so I, it raises the question of how are, how are these microbes even colonising the urinary tract.
So, you know, whenever I tell anyone about what I do, usually there are Their immediate reaction is, hey, wait, I thought that urine was sterile. Like that's even what I learned in vet school not that long ago, and it's really a shift in thinking to start saying no, urine, even in healthy individuals, even in the absence of infection, it's actually probably not sterile, and so We then need to figure out how are these microbes getting there, and one thought is that they're coming from the gut, that there can be sort of contamination of the perineal region and ascension of microbes, and that is likely true, at least in part, they can be coming from Other skin commensals, the urethra, the genital tract. There's even some thought, although not a lot of evidence about this yet, but some thought they could be translocating from the gut through the bloodstream into the urinary system, but that, again, we need more data about.
So, . So the, the way that they have to get there and the hurdles that they encounter probably really are is gonna dictate what types of microbes are, are able to thrive in that community. And it's, I suspect, a much more challenging environment to live in in some ways than in the gut.
Yeah, great. So it's one of these, watch this space, but probably you're in, as you say, not as tal as maybe we thought it was. So, yeah, that's interesting in itself.
I mean, look, thinking of, you know, we're talking about that's the, the normal scenario, the normal situation, particularly for dogs. What type of disorders are we seeing though when the dysbiosis is occurring within the, the kidney system, within the urinary system? Yeah, so there's several disorders that have been linked to urinary dysbiosis, many of those in humans, but some of them that we've identified in animals too.
So in the human world, there's been a lot of work looking at This urinary dysbiosis, in the context of neoplasia, so certain types of bladder cancer, urinary stone disease or urlithiasis, urinary incontinence, idiopathic cystitis, and, and several more I would say. In the animal world, we really have Just started looking at it kind of getting beyond the healthy dog or healthy cat step. So one of the areas where I am focused in with my personal research is urinary stone disease.
So I look at the urinary microbiome in the context of calcium oxalate stones in dogs, . We have had some what I think are very interesting findings there, so there's one small study that's already published where . Some of the bacteria, one in particular called a Cynoobacter, that was overrepresented in the urine of our canine stone formers compared to stone-free dogs.
That's also a bacteria that's been identified in some human studies as being enriched in the urine of stone formers. There's also some other trends that we're observing that sort of parallel what's been observed in the human world and stone disease. And so, Right now, this is really, it's very challenging to know what to do with this information because there's a bit of a chicken and the egg situation where we say, OK, well, are the stones making the microbes change or are the bacteria.
Causing the stones to form or what's happening. And so we have a long way to go to try to figure out some of those questions, but it's, it's an exciting start to see some of these parallels even across species, it. It makes me hopeful that there's something truly happening there that we can try to get to the bottom of.
There are some other groups in the veterinary world looking at the relationships between bladder neoplasia, so urothelial carcinomas and urinary dysbiosis. So I think that's very exciting. And then a little bit of work with recurrent UTIs and urinary dysbiosis.
And is there evidence, you know, thinking something like cats obviously very prone to chronic kidney disease? Is there anything at all being done on that so far, or is that still an area that needs a bit more investigation? Yeah, that's a great question.
So we have such limited data in cats, but we do actually have a little bit of data looking at the urinary microbiome in cats with chronic kidney disease. So, so I think you are not alone in having your brain go right to it and say that seems important. Somebody else thought the same thing.
And, and that was, that was not my group. It was a really cool study though they looked at cats that had chronic kidney disease, cats that had positive urine cultures, and cats that had FIC, and they found that there were These different, what they call eurotypes or basically different subtypes of what that microbiome can look like, and there was a lot of overlap between the cats that had CKD and the cats that had positive urine cultures with this escaricie like eurotype being the more dominant one. And so I thought that was really a, a very interesting finding and, you know, in humans, particularly human women, they tend to see more E.
Coli dominant eurotypes and in elderly women, and so, I thought this was interesting since our CKD cats also tend to be older. So, so yeah, just a little bit though, and I know there are a lot of people really excited about that area, so I'm hopeful that we're gonna start getting some more data about the CKD question too. Yeah, no, that sounds really good, but again, I suppose it goes back to what you said at this stage.
We don't know if it's the disease that's causing that difference, or if the, the bacteria sort of contributes to the disease, that would be really interesting to see how that goes. Is there any evidence that disrosis in the gut, may also have an effect on the kidneys? You spoke earlier about, you know, potentially the bacteria coming in from the gut, but Is there any other overlap from what you understand so far?
Yeah, so, again, these are such fun questions, . There are a few ways that we, we think that gut can be affecting, like the gut microbes can be affecting the urinary system in general. So one like, like we already talked about is, can we actually have direct transmission of microbes between sites.
So, so possibly and, and I would say probably even, beyond that though, there are a lot of other ways it can be relevant, so for instance, I can give a few examples. If we take the example of chronic kidney disease, we know that there are certain microbes in the gut that can actually produce uremic toxins, and so there's some thought that microbes can actually contribute to CKD and vice versa, it's a little bidirectional. CKD could actually then further contribute to this biosis and you get this sort of sad cycle, .
So that's one example of, of different ways that the gut microbiome could affect the renal system. We know it can do good things too. So, for instance, short chain fatty acids, which are a metabolite that gut microbes produce as they metabolise dietary.
Fibres, short chain fatty acids have all kinds of systemic health benefits, but they have been linked directly to the urinary system and even been shown to reduce some inflammatory responses in certain types of kidney disease. So it can have both positive and negative effects, . The other big area that I think we've got some data on about how the gut microbiome interacts with the renal system is with urinary stones, which again is where I'm interested, but that really started, a long time ago because people became interested in oxalate degrading bacteria in the gut.
And they were thinking, hey, I wonder if people who form oxalate-based stones like calcium oxalate stones, if they are having less oxalate degradation in the gut because of the deficiency in these microbes, and so that sort of started this whole train of thought where people were looking at oxalate degrading bacteria and that's really evolved and, and now I think we know it's It's less related to very individual oxalate degrading bacteria, which is what we first thought. So it was like this bug called Oxalobacter everyone was really interested in. And now the focus has shift more to these networks of bacteria that can do different things like degrade, oxalate, but there's a lot of other pathways we think are relevant to stone formation too.
So, Sort of like every day we're learning something new, so. So it sounds like it's not ridiculous to think that diet or things that an animal is given to eat could then go through and have an effect. I mean, obviously, you know, we've already got diets for kidney disease in the animals, isn't it?
So yeah, that. That sort of makes sense from that point of view. And I suppose that sort of perhaps leads us on to what practitioners can do.
I mean, I know you're saying a lot of this is in its early stages. I mean, are there any diagnostics or treatment options already out there, that have been validated and, you know, it's useful for the practitioner to know about? Yeah, so that is really the important piece here, right?
I would say. I don't, I don't have a lot to give you, but I can give you my 2 cents. So in terms of diagnostics, particularly, yeah, we'll, we'll start with diagnostics and then we'll talk about what you can do.
For the urinary microbiome, the, the short answer is no. So I would say we're, as I mentioned, we've got sort of this broad range of what's normal, but We need so much more information right now and so there's not a clinical diagnostic test that is validated and I think interpretable that that I would recommend for assessing an individual dog's urinary microbiome because You could, you could just send me a report of a dog's urinary microbiome, and I, I wouldn't know what to do with that information. It would depend on so many more things.
So, you know, there, there's that. I don't. Know how far along it will be before, if or when we have something like that, but I think we're learning a lot really quickly.
So hopefully there is something in the future that could be used as a diagnostic tool, . For me, clinically, there might be certain triggers where I would start to worry that a dog had an abnormal urinary microbiome, even if I'm not able to do a super quick test to, to confirm that. So one is that The, the risk factors for dysbiosis in the urine are likely the same as they are in the gut.
So the big shining example of that being antibiotics. And so if I have a patient who's had a lot of antibiotics that there might be a little part of me where I say, yeah, you, you probably have an abnormal microbiome, I, I suspect. Similarly, if they have Clinical signs of urinary tract disease, whatever those might be, whatever, you know, lower urinary tract signs, that might be a concern for me that things could be abnormal for, for all kinds of different reasons.
Yeah. The Reality is we're pretty limited in what we can do to specifically address the urinary microbiome now. What I do therapeutically is, and it's, it's very case dependent as you know, but My general strategy is, I think that promoting a good gut microbiome, which we know a lot more about with diet and things, is probably going to be beneficial to the urine too, because we know there might be some crosstalk between the actual microbes, so we want the happy microbes to be there.
We also know that The gut microbes can produce things like short chain fatty acids that have positive downstream effects on the urinary system. So for me, . You know, trying dietary strategies, fibre, prebiotics, probiotics, trying to avoid antibiotics, all of those sort of general strategies we use for gut health, I think can be beneficial for urinary health too, with the caveat that we have a lot less evidence to support it.
But it's not gonna do any harm, is it that kind of approach. And, I mean, it's interesting you talking about the, the short chain fatty acids that came out again in the, in previous podcast talking about gut, the guts and behaviour and things like that. So they, they're obviously ones to watch.
They are. And that's another area I'm very interested in. So I always have to reel myself in a bit when I start talking about short term fatty acids, so I don't go off the deep end, but they They are a good one to watch.
They're a very well studied metabolite, and we, so we know a bit more about them than other ones, you know, the gut is so complex with all the different metabolites and bugs there and everything. But, but yeah, short chain fatty acids, I wouldn't be surprised if they came up in a number of these conversations cause they just have all kinds of different applications. Yeah, that's good.
So there are some things though that the vet, the vet can do there. I mean, you talk about diagnostics being there yet. I mean, I suppose things like sequencing and things like that is just not practical at the moment for, you know, the vet in in the in their sort of everyday life.
But, is that something that can be done or is that not really an option on the genetics? So that's, that's a great question. So we, we do the sequencing for our research purposes, and The, the challenge with using that as a clinical diagnostic tool is that you just get one dog and so, When we're doing it for, for say a research study, we have a whole population where we're comparing, say, a group to another group or something like that.
And even in those scenarios, if you picked one dog out of the bunch and just looked at it, even with all the rest of the study data, it can be really hard to interpret. So, So I think we're, I think it is possible that sequencing will be a potential diagnostic tool at some point in the future, but I'm not sure, like I think that could be a long ways down the road, and I think what's tricky is how we would validate that. The other tricky part with urine is The samples are very low biomass, so there's bacteria there, but there's very few compared to what's in the gut, where it's just chock full of them.
And so the technical aspects of sequencing it are very challenging, . So, another avenue that I, you know, is possible in the future outside of sequencing, is in the human world, they'll do these what they call equaks, which are expanded quantitative urine cultures. It's basically They do yarn cultures with where they are able to increase the sensitivity of microbes they can detect by using a bunch of different culture media, different atmospheric conditions, they incubate it longer, bigger volumes, all that fun stuff, and they can detect a lot more, and so it's not.
As sensitive as sequencing is, but you also know you're detecting viable bacteria. And so that has been a bit more popular in the human realm, . Again, using it clinically as a diagnostic tool though is very, it makes me a little nervous because what I don't want to have happen is if people start seeing all these bacteria in the urine that they're unaccustomed to, and it prompts more antimicrobial use, and then we get into challenges where we're not demonstrating good antimicrobial stewardship.
So, So I think before things roll out as clinical tools, we just we just have a lot. More to figure out, probably in a research setting, so we don't sort of put the cart before the horse. Yeah, sure, no, that's a really interesting point actually, isn't it?
Because I think stewardship is getting better, but there has been that tendency to sort of reach for the antibiotics for any kind of infection and it doesn't necessarily mean it's . I suppose what you're saying here is the presence of bacteria doesn't necessarily mean that it's an infection that that it's a problem, is it, that it's, it's a natural, the natural sort of host day kind of thing. So, yeah, I think the, the messaging around that I could see being quite tricky, as you say, not to make sure that people don't overuse the antibiotics and, and make the problem worse in the long run, isn't it?
So, yeah, it's, as you say, chicken and egg horse thought you want to use, yeah. Exactly, exactly, yeah, and that's, if there was one thing for, for people to take away from this today, you know, it is the understanding that these, these bacteria can be good, they can be even preventing infections, keeping pathogens at bay by competing with them for nutrients and things. And so, so just observing bacteria doesn't mean we need to kill them.
Yes I mean, you've already talked about some of the areas that people are looking at. I mean I suppose if you're future gazing, what do you think the sort of next development's gonna be or the next discovery around sort of the microbiome and the interaction with the kidney and urinary system. Yeah, boy, there's so many directions it could go because, because we are so early.
So I think one important area that you've already touched on a few times is the relationship between diet and the urinary microbiome. We, we have one small study that is a very, you know, preliminary pilot study, that we're hoping to get out into the world looking at this, that, I think gives a little indication that there are relationships between diet and the urinary microbiome, but this is an area that I think is so practical to to have a better understanding of because we wanna diet is. You know, something we can manipulate readily, especially in our patients.
We know it has tremendous impact on the gut microbiome. There's been so much work studying those relationships that I think it's Really an exciting area for us to move into next is better teasing through how diet impacts the urinary microbiome and urinary system health in these different ways. We also, I think, you know, need to just on very basic levels get More data about what is healthy and what's happening in different disease states and start to move to the next step of rather than just observing.
Hey, with stone disease, we see these bacteria and in healthy dogs, we see these bacteria. Try to take it to the next level of understanding the mechanisms and what's actually happening functionally with those bacteria to tease through. Are they contributing to disease?
Are they protecting from disease, or are they themselves a consequence of disease or some other variable, are they a consequence of how we treat the disease, you know, there's just so much to to try to understand there. So, so I think that's another direction is gonna be, you know, mechanistically breaking down some of these things that we've just observed so far. Yeah, yeah, that's really interesting.
Thank you. Well, a really good interesting chat there, Emily, I've certainly learned some things there and I mean, I think sort of summing up what we've talked about today, for a start, it's looking at the bacteria you've got and say reminding people that yeah, it can be good and not necessarily reach for those antibiotics straight away and try and keep that healthy, healthy system in the. In the meantime and that idea of diet being a nice practical thing that it's not too interventionist, so using your pro and prebiotics, getting your fibre in there, all those kind of things that can, something that people can do now, that's really good and then.
Yeah, really interesting to see what's coming and like you said, there's mechanisms and how is this actually all working. We can see these balances being different between different disease states, but what does that actually mean? I think that'll be really interesting to see that coming up in the future.
So that just leads me to thank Emily for her insightful views and hope that giving everyone a bit of food for thought about the microbiome and kidney disease. Thank you, Emily. Thank you so much.
