In this series of three podcast, we will be discussing the complex world of the microbiome, the diseases and disorders that can occur when it it is disrupted and what the emerging research is saying and what practitioners can do to re-establish a healthy bacterial balance in their patients. This series is sponsored by Protection Veterinary in partnership with the British Veterinary Association. So today, in this episode we're focusing on obesity and diabetes and how the microbiome interacts with these to change these states.
We'll discuss whether this biosis might be linked to obesity and whether there are differences in those animals that achieve diabetic remission. From a bacterial point of view, we'll also look at the role of supplements and diets and the interplay between metabolic and endocrine disease and food and obesity. So today, I'm pleased to say we're joined by Ruth Costello, senior lecturer at the RVC.
Ruth's Clinical Interest and Research focuses on feline diabetes, Melati and di diabetic remission, including the genetic contribution to diabetics and cats. So welcome, Ruth. Thanks very much for joining us.
Thank you for having me on the podcast, Suzanne. Absolutely. It's great to have you.
So I suppose what would be really useful is just really to start with the the basics of, you know, the microbiome and dyb IIs and what that that is and so practise. Because I understand that, Yeah, I think that's a really good starting point. So when we talk about the microbiome, what we're referring to is the complex microbial ecosystem that resides in a set environment.
Now the mammalian body has a variety of microbiomes at different sites, but by far the biggest is the gastrointestinal microbiome, and the gastrointestinal microbiome is going to be formed from thousands of microbial species, and the combined genome of that gastrointestinal microbiome is going to be tens, if not about 100 times greater than that of the host. So we're looking at a very substantial microbial population, and that microbial population is almost entirely formed from bacteria. More than 98% are going to be bacteria, but it's also going to include protozoa, viruses, fungi and a relate a group called the Archaea as well.
And, when we talk about the Microbiome, people might have heard the terms microbiome and microbiota used interchangeably. There is a subtle difference between those two when we talk about the microbiota, what we're talking about is the taxonomy of the species that are found in a location. So basically a list of, the species who are living in that location.
So microbiota is often referred to as who's here. Whereas microbiome, is, refers to the combined genome of the microbial species in that location and that will include functional genes of, which the microbes are, using to create proteins and other substances. So the microbiome, is often referred to as who's here and what are they doing to And this, huge microbial?
habitat, is very metabolically active and therefore has been proposed to have a big influence on the host both in the gut and systemically as well. And if you read a lot of review papers on the gut Microbiome, you will see that some very eminent authors in this field, suggest that the gut microbiome is actually, considered to be a an extra metabolically active organ in the body because of its, metabolic capabilities. Yes, I have actually heard that about it being referred to as another organ.
But that's really, yeah, Interesting. And I really like that description of, who's here and what are they doing? That's a really nice way of thinking about it.
I mean, I know your particular area is cats, so I mean, I think we'll probably be focusing on that. But you know, if there's information about dogs as well, at this point, you know, it'd be really useful to hear about it. So I suppose as far as obesity and and diabetic, states as well, I mean, is it different for dogs and cats?
From what we know, what what What do we know about that? So far So a lot of the initial interest in analysing the gut microbiome in both obesity and diabetes has stemmed from human medicine. Because it's been increasingly recognised that both being overweight and having diabetes is associated with dys biosis in the gut.
Microbiome and dys biosis really refers to derangements in that microbial homeostasis that's going on, in the gut microbiome and that dysp OSIs could refer to a number of things. It could be that the proportions of the normal bacteria are altered. It could be that, one bacterial type becomes more prevalent, than others.
Or it could be that, functionally, those bacterias metabolism has changed. And, that that change in metabolites could have both a local effect and a wider effect on the hosts. Systemic health.
Now, there are in in people. That it it has been noted that, both, obesity and diabetes are associated with dysprosium relationships or simply an association. However, there is some evidence to suggest that, changes in the microbiome could be contributing to the development of obesity and type two diabetes in people and therefore could be, doing so in in cats.
And now, dogs we don't tend to think of as having type two like diabetes. That would be more similar to, maybe a type one like form of diabetes. However, even in people with type one diabetes and dispos has been noted.
And what will There are a few common themes. That, in, people, with both obesity and type two diabetes, which I suppose is is more my area of interest and is very pertinent because it's, has shares few similarities with our diabetic cats. And, what will often be shown is that these patients do have a, decreased, diversity of bacteria in their gut.
But there are also a few, bacteria, file of interest when it comes to development of obesity and also, how the microbiome might be affecting a patient's glucose homeostasis, and And we we can run through those because they'll often be, the things that are particularly noted in any human or this the emerging veterinary research, on how the microbiome might be playing into both patients developing obesity and diabetes. Melius. So there's a, a few sort of particular, bacterial tax of interest.
Sometimes when we're looking at, the effect of the microbiome on obesity or diabetes. And, the first of this is, the bacteria that are capable of producing short chain fatty acids. Now, short chain fatty acids.
Ha are a very important, we believe, metabolite that stems from the microbiome. Basically, the common short chain fatty acids are butyrate, propionate and acetate, and they are largely produced by your microbiome, from non digestible polysaccharides. So one of the real interesting things about the microbiome is that, because this is a huge, microbial population with a very different genome and metabolic capabilities to the host.
That, bacterial population actually gives the host access to a lot of metabolic pathways that aren't actually common to their own species. And, some of these metabolites produced by the MICROBIOME are thought to be particularly important both in gut health, but also in other aspects of the host health. One of these really important areas is, this short chain fatty acid, producing bacteria.
Now, these short chain fatty acids have a huge number of, potential use beneficial effects to the host. For starters, they are, an extra energy source, for the host. However, and they are particularly an energy source for the gastrointestinal colony.
They also are, we believe, are local regulators of gastrointestinal motility. Producing short chain fatty acids in normal quantities is also meant to keep in check, and sort of more pathogenic enteric bacteria. But some of These short chain fatty acids are also thought to have anti-inflammatory prop properties, both locally in the gut but also systemically.
And that's particularly the case, for, butyrate. And what's more, it's also hypothesised that butyrate, might also have a role in promoting insulin sensitivity in hosts and what we'll find in a number of, studies. Especially in people, is that butyrate producing bacteria seem to be decreased in individuals with type two, like diabetes melat.
So the short chain fatty acids are beneficial for our local gut integrity and health, but also might be having these anti-inflammatory and insulin sensitising properties, in the body as a whole. And they're often one of the focuses, in these, M microbiome analysis in patients with diabetes or obesity. Another focus is bacteria that are capable of transforming, bile acids from primary bile acids to secondary bile acids.
These secondary bile acids can also have a number of really beneficial effects. Not only do they so help, keep in check more pathogenic enteric, organisms. But they also, when absorbed, are believed to have insulin, sensitising properties and to have several beneficial effects on glucose metabolism.
The exact mechanisms by which they do that are not very clearly understood. But we believe that they could be involved in, up regulating insulin secretion from the pancreas, for example, and could well be involved in in promoting secretion of a hormone called, Glucon like, polypeptide one from the intestinal tract. Now that's known as one of the incretin hormones.
And these are gut derived hormones that, can have, wide ranging effects on both glucose homeostasis and satiety in hosts. So promoting release of that in, O, obese or diabetic patients is a is a very beneficial, action. And, these, and G LP one has recently been in the news a lot because, it's the hormone that the the new weight loss drug, is based around, so people may well be, familiar with it from that.
And basically what that weight loss, treatment is trying to do is to mimic the action of this natural and credit in hormone G. LP one. Yes, certainly.
I think the mention of the Vanity Fair gala dinner or something wasn't it? There's a lot of that about, the short chain fatty acids. I think that's really interesting.
This is certainly not the first time it's come up on the podcast. They seem to be quite key in a lot of areas associated with the microbiome, Not just the gut one, and again really interesting. The idea of, you know, endocrine hormones, affecting your your safety and things like that.
It's really interesting, Ruth, so I think from what you're saying, is it if you're getting, a cat that's going into diabetic remission, will you find that they will tend to have a different microbiome to the ones that don't Is that we got to that yet or not? We have not got to that yet at all, unfortunately. So, and they will be a wonderful population to study.
Because the the research into microbio analysis in in our veterinary patients is still really quite early on, compared to people. Yeah, and, what we, what has been looked at is some few initial studies comparing diabetic cats to lean cats or diabetic obese, diabetic cats to, obese cats. Who are non diabetic.
But it's yet to be looked at whether, the microbiome might change, in remission. And they would be a really good, group to look at, because obviously they they'll they'll should be acting as their own control. And, that's certainly something that our research group here is hoping to look at in the future.
As we we have, potential samples that could help answer those questions. Yeah. Yeah, definitely feels like an emerging area again across all the people that we've spoken to.
I mean, perhaps we continue with diabetic cats. I mean, are there things that the the practitioner can do? I mean, there are there foods or supplements that that seem to be helping again?
If we we got evidence yet on that, Unfortunately, we haven't got much evidence on that yet, either. Now, there really has been very little research on, how the microbiome might alter with different diets in diabetic cats. One study did place diabetic cats on a higher protein, carbohydrate restricted diet, and but didn't actually find that the microbiome changed, in those cats.
As they were sort of introduced to that diet over four weeks. Now it might be that that was too short a time frame to see any difference, or it it can be, Microbiome. Studies can be, sometimes challenging to conduct and, assess because of, a variety of factors that can can play into both the samples we're using and also the methodology that we're using to to look at the, samples.
So there certainly are, plenty of possibilities with how diet might alter the microbiome and how that could theoretically have beneficial effects. For feeding overweight cats or, diabetic cats. Anything we can do to, in people the sort of things that have been tried have been to use prebiotics or probiotics to help, with these, beneficial microbiota effects especially, short chain fatty acid production.
We're not quite there yet with that with the evidence with diabetic cats as to, seeing how that might impact the microbiota, what would be what will be interesting in future, I think, is not only to look at how, diet or remission or other changes in diabetic control impact the microbiome, but also what the microbiome is doing and the functional side of the microbiome. And for that, we may need to use different techniques. So advanced genetic techniques such as DNA shotgun sequencing might provide information about as well as who's there?
What functional genes they're expressing. So what are they doing to, and help us show that whether even if the proportions or the abundance of these bacteria aren't changing, is what they're doing changing. And that Is that why at the moment in those early studies, we haven't seen a difference, in the microbiome of of diabetic cats undergoing diet change.
But it would also be possible to use a technique called metabol Loic in patients, to try and understand whether even if the microbiomes proportions are not changing whether they're doing something different and metabol omics refers to, taking a sample and looking at a vast array of metabolites. In that sample, it certainly would be possible to do something like that on the sea of diabetic cats going into remission and see whether any identified metabolites that could be of microbial origin in the gut are changing, as as the patient goes into remission. Now, one, downside of the short chain fatty, as we've been talking about is that they can be very difficult to identify in clinical samples.
They're very volatile, so identifying them in faeces is difficult, and also a lot of them are removed in first part through the liver as well. So, the concentrations in patient serum might not actually, reflect what's coming out of the gut in the portal blood supply. And but looking at, the transcriptome So what?
DNA is being used to produce proteins and other metabolites by the microbiome using advanced genetic techniques. Could be, of real interest in the future to try and understand the actual mechanisms by which, the microbiome, even if it's not changing itself, it might be changing what it does during these, patient, the patient's journey into remission or a patient's journey on weight loss. Yeah.
Oh, that's really interesting. I really like the idea of being able to delve in there in the genetics, so I'm sure it will get there eventually. And I mean, as you say, Not yet.
They're the evidence. But it might be that Yeah, there might be an opportunity for practitioners to change the discussion, you know, perhaps more around dietary management rather than sort of weight management or something like that when it comes to these kind of animals. So, yeah, I see it being a good way.
You know, obviously, bes is a great problem and and, you know, diabetics and cats certainly seems to be, a problem as well. That's on the rise. So anything that can help practitioners with that in the future, I think would be very welcome.
Yeah, and it's quite a big topic in people as well. There have been initial studies using prebiotics and probiotics to try and improve glycemic control. And there have been some positive effects seen.
And it is also proposed that maybe, it's not entirely something like obesity itself that is contributing to insulin resistance. Maybe it is the types of diet that predispose to obesity that are having a direct effect on the microbiome, or gut permeability, for example, and that is contributing to the inflammation that we can see in obese patients, which, certainly in people can then lead to them becoming insulin resistant and developing diabetes. So maybe it's it's not simply the weight gain.
It could be what individuals are eating as well. That is leading to this diabetes pathogenesis. Yeah, yeah, really interesting stuff.
Thank you. You've told us about research that's happening at the moment. Is there anything else that you think's got real potential that people are trying to look at at the moment in this area?
So I think the the the big air of potential could come back to this. These metabol Loic studies looking at how, this huge, vast array of metabolites in patient serum and and those that might come from the gut. might influence, have wide ranging systemic effects in the host.
That can be done on quite an exploratory basis. So people will look at sort of use non targeted metabolisms, looking at a huge number of different metabolites in different disease states. And then in trying to interpret what they found in relation to what you know about the patient's phenotype, and that's been done quite a lot of different veterinary diseases.
For example, chronic kidney disease. There's various papers on that cardiac disease, a few obesity papers, including in cats. But I think what we are lacking is those, big exploratory studies in diabetic cats or maybe cats who are undergoing weight loss as well and looking to see how things change.
So I think it's it's definitely going that sort of research is definitely going to be coming in the near future. Because it's very much an emerging field, and there are an awful lot of papers that have been published in it, in in the last few years. Yeah, great, thank you.
Well, I think that brings us to the end of our time, re so that's, of course, whizz by it. And I think you know, really interesting things to talk about them and again, another area where it's very much, you know, emerging research and trying to work out the cause and effect and what's going on there. I really like that.
This idea of you know not only who's there but what are they doing? I think that's really interesting and perhaps gives a hint as to why some of the results that we're seeing so far, perhaps haven't quite, you know, married up with what people might be expected there. So yeah, really interesting.
Although it must be said that even though we're in a very early stages of veterinary research, there are hints in those early papers that, show some quite interesting stories. Regarding findings and how this might fit in with gluco toia, Stasis or, the presence of obesity and a a few things that are mirroring what's been shown in the much wider body of human literature. So I think this is definitely something that is warrants further investigation in the veterinary field.
We've got some really interesting early results, and eventually this could well translate into treatments that are targeting the microbiome in the hope of having these more beneficial, systemic effects in people. Just like they're trying to bring out in, sorry in animals, just like they're trying to to bring out in people. So I think it's definitely an area that's going to grow in the next few years.
One to watch if you're a practitioner from the sounds of things. Absolutely. Yeah.
Brilliant. So thank you. Ruth for the informative discussion.
I've certainly learned something again today. And, I think hopefully given everybody something to think about with the chunky issue of managing diabetes and obesity. And cats, particularly, and dogs too.
So thank you very much. Thank you very much for having me on the podcast.
