Good evening everyone and welcome to tonight's free webinar. The topic tonight promises to be a very interesting one. We're looking at new insights into probiotics and microflora.
We'd like to thank Purina for their generous sponsorship, which allows us to bring you the highest quality CPD completely free of charge. This webinar is part of a series of webinars that we have been, producing. In collaboration with Purina, and we've had some excellent talks from the like of, Francesca Gazaniga, Xavier Menteca, Holga Volk, and plenty more which are on our website, and they can be found there if you go to the webinar vet.com.
I'm going to pass over to Libby Sheridan, who's on the line from Purina, who just wants to say a few words before we begin. Thank you very much, Paul. Good evening, everybody.
I'm really excited to speak to you this evening. I'm just gonna take a few minutes to introduce you to a fantastic new resource and, of the Purina Institute. This is something that will be accessible to all veterinary professionals in practise.
So just to outline to you some of the really good content that is in there now. So the Purina Institute, has been launched just at the end of last year and with the purpose really of bringing some really, In depth and educational science, nutritional science, and to all veterinary professionals because we believe that science is more powerful when it's shared. So as well as sharing our groundbreaking research, we're also going to help you to access objective fact-based nutritional information that's sourced from the whole scientific community as well and on trending topics and nutrition, just to keep you bang up to date.
. So just to give you a little bit of background about the Purina Institute. So we're focused solely on the science. So what you won't find in the Purina Institute resource will be information on products or product claims of that kind of thing.
You'll be able to find all that on the, the Purina Nor website, but the Purina Institute is purely focusing on the science and really it's so that owners of pets and the pets themselves can benefit from this, from this really, advanced, research that's going on. So it takes 3 pillars in the Purina story, so leadership and science, and scientific expertise and resources, and then innovation and collaboration. And just to go through these quickly.
So leadership in science, Purina has been a leader in nutrition now for, over a century, and we've helped to bring some of the major breakthroughs that you take, probably every day that you're using in practise. We help to bring those to life. So starting right back in 1926 with the first research centre that was dedicated to dog nutrition.
Through to the first company to add taurine into dry cat food, and the first, company to bring weight loss diets that use the high fibre approach and then the high protein approach, and you'll probably all be familiar as well with the body condition scoring system, which was, first of all, brought to fruition by Purina. Thereafter, we've been innovating throughout the decades. The first and only veterinary prescribed gastrointestinal diet, to use medium chain triglycerides, the very first hydrolyzed diet, which was Purina HA as well, and right through to more recent innovations such as the neurocare diet that helps animals with advanced cognition deficits.
This just references a study that you'll probably, if you don't know the study directly, you'll certainly be familiar with the body condition scoring chart that came out of it. So the nine point score and that was based from a longevity study with Labradors, which proved that, keeping, a dog at its optimal lean body condition can extend its healthy life by up to 2 years. So quite significant results from that study.
And followed by another 9 year old study, 9 year study with cats showing that a blend of nutrients can help extend a mature cat's healthy life by up to a year. So certainly kind of studies that have been followed with a long term commitment to bring these great findings to the fore. We also, I just wanted to give a little bit of background on our scientific expertise and our resources.
So Purina, has got a huge number of scientists, right across the globe. We span 5 continents and we have a team of vets, nutritionists, communication specialists. And, and marketers as well to help bring this information, this pure science right to your door.
And, so we have an extensive network of 8 R&D facilities around the world, as, as it says here, over 100 years of research, with over 500 published papers in scientific journals, and we've currently got, nearly 8000 granted and pending patents worldwide. And these are just some of the topics that you'll be able to find once you go into the Puring Institute. You'll find a whole resource archive in there, including papers, published papers.
There are videos, there are loads of educational tools in here and you'll find that they're cross. All sorts of innovative topics. The areas that we've been particularly focusing on lately have been with brain health and showing kind of that a specific brand blend of nutrients can help, really, enhance the quality of life of dogs with cognitive dysfunction, gastrointestinal in there, and molecular nutrition as well.
So if you're interested, particularly in the whole science around the gut, A microbiome, around the gut brain access, all those kind of things. There's some great information in there as well, and it would be so good to hear more from Mike on this topic this evening. Beyond the resource hub that's there, we also have an advisory panel, which are constituted of key opinion leaders from around the global community, and they're helping to kind of, input into all this great wealth of material for you.
We also support and sit on the WSAVA's Global Nutrition Committee, and we also are a major sponsor of the One Health and the One Care initiative. We have existing partnerships all around the globe with a lot of key opinion leaders and host conferences and symposia all around the world. So I'm really looking forward to hopefully see you coming online and, and accessing a lot of these great resources which there's content of the Purina Institute.
So this is where you can find it all. So on Purina Institute.com.
And so you can just go on there. It's really, really easy to access and you'll be able to use it on your desktop, on your mobile, on your tablet. So, so whenever it really suits you, and you'll be able to dip and dip out of it as, as, as you need.
So I'm going to wrap up now and I'm gonna hand them back to Paul and to Mike, and thank you very much for your attention. Thank you so much, Libby. That's a really, really fantastic, presentation there.
And it's a really great insight into the, the past and the future of Purina. It's a wonderful resource, one that I think will be really useful to vets. Onto tonight's webinar, we're just gonna do a very quick, piece of housekeeping.
So if you do have any questions that you'd like to submit to the speaker, if you hover your mouse over the screen, you should see a black bar which includes a Q&A box. If you type your questions into the Q&A box, We will collate them and work through a number of questions at the end. If you're having any technical issues, please do submit them into the chat box, myself and my colleagues are online and we'll do our best to make sure everything's working properly for you.
So on to tonight's webinar, we're very excited to have the extremely knowledgeable Doctor Mike Lapin presenting. Doctor Lappin graduated from Oklahoma State University and then completed an internship, internal medicine residency and PhD programme in Parasitology at the University of Georgia. His principal areas of interest are prevention of infectious diseases, the upper respiratory disease complex, infectious causes of fever, infectious causes of diarrhoea, and zoonosis.
Doctor Lapin is the Kenneth W. Smith Professor in Small Animal clinical veterinary medicine at Colorado State University, and he helps direct the shelter medicine programme. Doctor Lappin is also the director of the centre for Companion Animal Studies.
Recent awards include the Northern Distinguished Teaching Award, the European Society of Feline Medicines International Award for Outstanding contribution to Feline Medicine, the Winn Fein Research Award, the ACVIM, Roberts W. Kirk Award for Professional Excellence, and the WS AVA Scientific Achievement Award. So enough from me, it gives me immense pleasure to hand over to Doctor Mike Lappin.
Thank you, thank you, Paul, and Libby, what a great introduction about the institute. Fantastic. I'm, really honoured to get to lecture tonight and to have materials that we can add to the Institute, educational files.
I've been a Purina, Nestle Purina researcher for, many, many years now, but I spend half my time working with clinical cases in internal medicine and or at the shelter, and about half my time, doing research projects with a variety of collaborators, which we'll talk about in a few minutes. That primary email there on slide one, the Mlappin at Pollostate.edu.
That is my functional CSU email, and I, as you might guess, giving it out at about 50 different meetings per year at the last 3 days in Warsaw, Poland. I give it out quite a lot, so sometimes I get a little behind and so please, if you don't hear back from me about this webinar within 48 hours, if you could please resend it and then put second attempt in the subject line so that I know that I missed one, and I'll try to respond promptly. We never mean to miss them, but gosh, there's quite the volume of emails these days.
So hopefully I'll be able to block out my Oklahoma accent today and and be a little bit more neutral. But before we get started, I might as well say, how y'all doing, which is how I was brought up. So I've been working now at CSU for almost, almost 30 years.
I, I started here when I was 12 years of age, and you can see in the picture on the upper left, that's Emily Cross. Emily is the liaison to universities for Purina Pet Care in the United States, and they've been working with us with the centre for quite some time. I'm actually, I greatly involved with the Purina Institute, and in fact, I presented there, just last Wednesday, and I hope you get to come over to Saint Louis sometime to see the facilities.
They are truly fantastic. But I want today before we start, just to remind you that all of us that work with companies like Marina that are totally committed to research being what you should present, I did want to let you know that we do have the opportunity to work with many different companies in the centre for Companion Animal Studies and, and how we can do. Research with, say, multiple pet food companies or take their donations is we just make sure not to do competing projects.
So as I talk about probiotics today, we won't just talk about my Purina studies. We'll talk about some of the other great studies that have been done with other companies over time. But the point is, Purina is a great group.
I have loved working with them, and this particular programme that they started several years ago, and I just was able to make another recording this year for the BMX meeting in Western Veterinary Conference. This lifestyle for them, the fact that they're making pet food that's backed up by research. As an outside person looking in, I really want to corroborate that to you guys, that they are quite fantastic, and of the pet food companies that I have contact with, they have really stood above when it comes to numbers of projects funded.
I think I published my first rea study about 15 years ago. Not all with probiotics. We do dietary management of diarrhoea and many other things with this great company as well.
But what I was gonna do today, and, and I think we've allotted about 50 minutes or so for follow-up questions today, live by computer and then by follow up by email at your leisure. But I wanted to make a few general points about how to choose a probiotic. I was lecturing at Western Veterinary Conference as well as the veterinary or VMX conference, the old North American meeting, this year, and there are literally hundreds of exhibitors, and many people are offering probiotics as part of their portfolio.
I'd like to talk a little bit about that with you today. About how you might want to choose when there's that many different products. I'm sure that London Vet Show this year and BSAVA what last week, probably had a number of people peddling their goods, so we need to pick the ways to make sure that we're getting what we're paying for.
And we'll spend a few minutes chatting about what we now know and dogs and cats about probiotic use and gastrointestinal diseases, and then we'll ultimately close out with the data as immune modulators. And remember, immune modulators could go either direction, either immune stimulation or perhaps immune dampening. And then foldger's, previous lectures on the new diets for brain health, etc.
Are also fantastic. So I hope you get to see some of those other lectures as well. So I think no matter where we're at, in the world, and I guess I was actually in London, yesterday for 2 hours on my way back from Poland, if we look at this slide, I think we would all agree, no matter where we're at, that these labels are on correctly.
The sooner we can go from a faecal score of 6 or 7 to a normal stool at 3, maybe even a a 4, the faster that happens, the better for everyone. Obviously lessening the animals suffering, but also Lessening the work of the family, cleaning up messes, lessened risk due to zoonotic diseases. And if you're a shelter, that working with rescue animals, the sooner they have a normal stool, the more likely they are to be adopted.
And so one of those pathways to try to speed resolution of diarrhoea has been, probably part of the wheelhouse of probiotics and small animal practise using probiotics, for gastrointestinal disease. So I think we're all familiar with the definition these days about, giving live microorganisms that might confer a health benefit. There have been some great reviews in the last couple of years, and I did want to show you Al's Jan's and Elena's review paper from that record.
If you didn't see this one last year, in 2017, it's actually quite fantastic, really good resource for you if you're interested in learning more about the microbiota. Today, we will focus on the GI part first and then we'll shift gears into immune modulation. Many of you might recognise I'm the Mike Lapin that first did toxoplasma, IGM, and IgG testing around the world, Fundamycin for toxoplasma.
I worked my way into. PR with chronic diarrhoea, worked my way into upper respiratory disease of cats, vector-borne diseases, and I'm actually also proud to be the Wassava One Health chair, and Purina is one of our best sponsors, of course. So why I mentioned those other more chronic infectious diseases is that I actually became interested in probiotics when I learned about Purina first getting ready to launch the strain of enterococcus fecium called SF 68, the probiotic bacterium that's actually in their commercial product, Fortiflora.
I'll tell you the story and show you that first paper that I was able to read before it was published, that got me hooked into this type of research, because I just look at all those animals that we have with chronic infectious or inflammatory diseases. And when I started to learn that by working with the microbiome, we might actually be able to immune modulate those animals, I actually became quite excited. So from today's lecture, I'll be able to show you my lectures on the GI type side of things.
We'll show you a few of the other studies that have been published that weren't from my group. This is not a Ana only lecture. And then I'll show you the immune modulation things, talk about the potential for the future and what we've proven, at least with SF 68.
Serena has been the most active in studying immune modulation and the stimulation side of the immune system, and I look forward to sharing that with you. So Scott's team, Doctor Weiss there in Ontario, he's actually done a couple of really great studies purchasing products that are purported to contain probiotics and I went ahead and just made a red box around one of the important points from this paper, that of the 19 products tested, 5 of them basically had no growth. And so these, these probiotics that were being sold actually didn't meet their label claims.
And in the UK as well as the United States, there is less regulation on nutraceuticals, food additives, things like probiotics, from our, regulator type people, certainly much less than, than the scrutiny that undergoes a label for an antibiotic. And so one of the first things that I do if I'm at a meeting and I'm learning about a new company or an old company with a new probiotic, first thing I ask is if they can show me or share with me their shelf life data. Proving to me hopefully that whatever they're claiming to be the shelf life, that they actually have data that proves that those numbers were actually present within the product in question, over that entire time period.
And what I think you're going to find, if it's like I've seen in meetings around the world, that many of the companies, even though they might be a big name company, they may not be able to answer that question. And so, gosh, if they can't answer that question, I'm gonna wander on down to the next booth at those shows and and look to see what other people have to offer. And so in the United States right now, we feel pretty comfortable that we've got 3 companies that have been able to consistently meet their label claims.
Now this biome that that's the old BLS number 3 with the new Canyon Animal Company. And then obviously Forta Flora, the heterococcus DM strain that's 68, they, they probably have by far more data than anyone else. And then the Neutromax folks, it's obviously a good company, and they've done a good job, at least proving that they have good stability.
The other reason that we like these three companies here at CSU is another thing for me is not just a, a researcher, but as a practitioner that does research. I really like the sport companies that support science. If they're funding projects with their probiotic, for example, that's, that just makes me feel more comfortable to purchase that one.
And so I'll tell you little stories about each of the three of these as we go on today, but you, visit us here in Colorado, sometimes in the next 2 or 3 months. These will be the only 3 you'll see us prescribing because right now our internal medicine group feels that data is the strongest 3. So here are some unanswered questions just to plant the seeds with you before we move forward.
A lot of the things that these types of products have on their claims. There'll be things like more is better, you know, we have more bacteria, either more strains of bacteria or sometimes more colony counts of a single bacterium. And those are the kind of things that are great.
You can say that, with, with food additives, nutraceuticals, probiotic type products, you can say some of those things without very little. From the scrutineers, but, you know, we frequently have no idea. I trust that Carina probably looked at multiple doses of FF 68 and showed the dose that they're currently providing in their canine and feline products are probably optimised.
They obviously want an effect at the best cost of goods for them. But then when you start saying, well, we have 6, so that's better than 1. That may or may not be true, because as we'll learn today, if you hadn't recognised already, you might actually have an immune dampening bacterium with an immune stimulating bacterium.
And so having 2 bacterium or 6 bacterium, you may actually be having some organisms combined together that might actually be counterproductive. And so how I feel about this is what we need to do. If somebody wants to say X is better than Y, then they need to have a study that proves that it's better.
Otherwise, you can just present what you have done, and that's how I purchase products. I want to hear what the company's done. If the company has compared to a competitor and shown it to be better in a peer-reviewed scientific journal, then I'll probably buy the better one.
But many times you're just gonna have to listen to what they have published themselves and then make a decision. And again, that's our purpose today together is for me to share with you, most of those recently published works. So I wanted to show you this one just as an example, not to pick on Nutriax or a fine company and their products are quite high quality, but I found it interesting that Endococcus specium is listed first on this particular ad, but it's not actually even the same strain that's in the Purina product.
Pria product is the only one to have the strain SF 68, which has had hundreds of papers published since it was first isolated from a child back in the 60s. So just because it says a genus and species, that doesn't actually mean that it's going to perform the same is that same genus and species that's a different strain. So right now, when we talk about the SF 68 strain, any of those publications would have to be considered unique to the 4 tolora product.
So let's do a little diarrhoea review and what's been done as our first group of papers. I assume that the UK clients are similar to those in Colorado. This was a picture that was sent to me by an owner, and she wasn't excessively happy that her cat spraying diarrhoea all over her floorboards, and certainly would like that to get better faster.
And so I actually believe when the question is asked of me, Does data exist, it would suggest that probiotics can influence the GI microbiome. The answer is absolutely. Today, I'll show you some of those microbiome type studies, but I thought it might be fun to start with a couple of the papers that were mainly basing an activity based on clinical response.
So this was one recently published by our group. This group of shelters, animals. We studied.
They, they did like to use metronidazole. That was kind of their non-specific diarrhoea, antibiotic. And as you know, we're trying to get away from that these days, using metronidazole only when we have a specific organism.
But since we happen to have metronidazole, kind of a requirement of that shelter. To get a design to try to tease out whether or not the Fortaflora probiotic, this is Purina's enterococcus VF 68. If we were going to tease out any data, we were able to get the shelter board and the animal board here at Colorado State who agreed that we could do a pilot study of 16 animals per group.
We did feed the shelter animals a standardised diet for the entire study. They did stick with their metronidazole protocol, and that was given to all the dogs in the study. And then we did a randomised study giving Fortiflora to half of the dogs in the placebo, to the other half.
We did use the Purina scoring system, 56, and 7, a 7 being water, we use just the abnormal ones. We wanted to get them back down to at least a 4 because most owners will adopt an animal if the faecal scores is 4 or less. And then we also looked to speed the improvement, basically.
I just wanted to use one of the charts from this grant, and project just to show, yes, the stool character over the course of this study was improved statistically compared to the dogs they got metronidazole alone. And so we have shown that metronidazole doesn't kill fortiflora. So in this particular study, we were able to give metronidazole and the SF 68 at the same time.
And because of this work, when I'm using metronidazole, say, for GR dialysis, I do actually generally prescribe SS 68 for those acute cases. Use it for the 1st 14 days or so. Interestingly, we seemingly had some trends, we can't say statistical, but we saw some trends suggesting that adding the 4tiflora with metronidazole might have been giving us some superior responses to those dogs that also had Giardiasis.
Now, what we're doing now is a follow-up study. We made it about halfway through the study last summer and we're continuing it. And hopefully at ECBIM or ACBIM next year, I'll be able to show you some more specific data.
But if you pull out one of the early rodents. Studies with SF 68 and Giardia. There's actually some method to this madness.
They've actually shown that fortiflora by itself could immune, increase immune responses to Giardia and decrease shedding in a rodent model. So right now, I'm a metronidazole plus fortiflora fan. This was one of our first cat studies.
We did dogs as well in this study. However, when we fed the shelter a standardised diet for the entire summer, the dog diarrhoea rates dropped to an extremely low level, though we ultimately were only able to show statistical differences in the cat groups. But this was an interesting one from the internal medicine journal, 7 years ago that we did with a summer student, my lead parasitologist in my research group.
And so what we did in this particular study was we fed one of the rooms, so this isn't an individual animal effect study. This is an effective fortiflora on a room. We fed one room fortiflora, the other room was fed the placebo.
And let me digress for one second. All of the SF 68 studies that I'll talk about today that were done by my lab, we don't actually use the sachets. The company actually sends us the probiotic in capsules, and then they send another group of capsules that have everything, the palatability enhancers, that tasty chicken and liver, hydrolyzates.
They send us those. But without the bacteria. But they send it to us either as blank capsules or capsules with a red dot.
And so we don't actually know which is which. And generally, we won't break the code to say, did a study work until the end. And also at that same time, I always reculture the probiotics to make sure that the probiotic has the label claim, as well as to prove that the control did not have live bacteria.
So that's what we did in this particular study. Here's the design. We had a feral room.
The kitten room was kind of our washout space, and then the stray room. And as you can imagine, cats that would be considered feral, a little bit more stressed, a little bit more parasitized. Stray kitties, though, the ones that might have just been found on the street and were considered nice, you would think they may be a little less stressed, but they were closer to the barking dogs.
So how we got around that is we did a one week washout after one month, and then we switched the rooms. And so for one month, the feral room was getting 4 of Flora, the other month it was getting the placebo and vice versa with the stray room. I don't want to belabour a paper that's 8 years old, but if you look at the results, the closed bars or the placebos, the open bars are for the flora.
And you can see the percentage of cats with diarrhoea for at least 2 days or longer was statistically lower when the stray room was fed for the flora. The feral room, it didn't quite achieve stat. Statistical significance, and when we combined all the data together, that statistical significance was maintained at the PE less than 0.05.
So this was our first study that I did with this probiotic in cats that made me pretty much consider using it frequently by pet cats. So overall, I felt, and this is what I told the company up front, is if we can show any effect in a shelter, that's going to be quite impressive because there are so many variables, or so much stress, etc. And so I actually believe this was pretty strong data in the Journal of Veterinary Internal Medicine, is generally a pretty well accepted journal.
So I think that's great. And so what I then do, I ask those probiotic makers, that might be trying to get into my clinic with product. Do you have any data of this?
Type that lets me, know that your probiotic might have an effect on acute, non-specific diarrheas. If the answer is they don't have that data, then I'm probably not ready to buy that probiotic because I already have data with Fortiflora, and it's in my country, and I know it's well tolerated and, very tasty. Now, this is one that you can find at other sites, at, at the Nestle, Purina websites, at least in the United States.
And I do believe Gale is going to publish this in the future. This is, some of those kitties that they maintain as taste testers that then ultimately get adopted as well. But, but these are kitties that have, less than perfect stools, and the darker the bar, the better the stool character.
And On these kitties were then supplemented with enterococcustaium, as you can see, the proportions with, with a better stool quality increased. So that's just more of that kind of chronic non-specific diarrhoea. I look at the shelter study is more of a excuse me, an acute stress type situation.
This is that kind of chronic idiopathic diarrhoea group of cats we see that supplementing seem to be beneficial. And then the power of open label trials generally is a little bit lower than placebo crossover type studies, but it is still a respected paper that the Muromax people funded. This was actually done also at Colorado State, just with one of my collaborators, Craig Webb.
And if you don't remember this paper, they took cats that had, non-specific diarrhoea that was certainly chronic. Most of the cats got a pretty good workup without a real obvious cause being found. They then supplemented, allowed the owners to, give all kind of those visual analogue scores, how well do they think their cat's doing?
Do they think the cat improved? And if you pull this one out and read it in depth, you'll find that about 70% of the owners were happy that they, . Use the probiotic and and this one was a Nutramax study, and 70% without a control group doesn't, you know, give you a lot to do statistics with.
And I think most of us feel that the placebo effect is only about 30%. And so it seemed like this probiotic, was doing some good. So, kudos to them for publishing that.
The next one that we did in my group with enterococcus VM strain FS 68, this one we wanted to do a study to see what happens to the microbiome when you give cats amoxicillin clavulonate, and also then to see if we could improve the diarrhoea that's induced by that antibiotic. As we know in the past, this causes diarrhoea for sure. We just didn't know a lot about what exactly it did to the microbiome.
So, Camille did this, she did her residency with nutrition with Purina's a partial sponsor. So I think Purina for that, summer research, fellow, and then this is Jan from there at Texas A&M. He did the microbiome work for us on this study.
So basically we decided since amoxicillin clavulanate actually kills SF 68, we felt that we needed to separate them, and in this case, we separated them by feeding the probiotic first so that we would hopefully have the probiotic binding its receptors starting to do its thing on the microbiome prior to the antibiotic. And then we also wanted to kind of fit with what an owner might be able to do if both family members worked by having the probiotic, like, right when you got up to feed the breakfast and the probiotic, and then going on to take your shower, come back, give the antibiotic, get the antibiotic again in the evening. So, we kicked out cats that looked like they had stress diarrhoea prior to starting the antibiotic.
Those that stayed in the study got 7 days of the antibiotic and 14 days of it. And if you haven't seen it recently, here's the classic Purina score system that most of us use in our studies. But if you look at the data at the top, is that impressive?
Look how many cats actually get diarrhoea due to clavulanic acid. Why I feel that we don't get that percentage of reports back from owners. I believe that many of those cats probably are a 5, and then with clumping litter, then the owners don't actually notice it's diarrhoea.
But it was a fact, greater than 5, at least. And that would be a 6 or a 7, at least 12 of the 14 kitties in both groups. So if we look then at those distributions of faecal scores, the statistical difference between the two groups, with the SF 68 being open, the closed bars being placebo, numerical trend, numerical trend, statistically different.
None of the cats that were fed SF 68 developed a 7. And then if we just look at the group being total diarrhoea scores, statistical trend, and then over the course of the entire study, statistical difference with the stools being better if they were to have SF 68. So we felt that that was pretty good information that suggests that this probiotic could lessen amoxicillin clavulonate diarrhoea, and that has influenced my personal clinical practise.
By now, if I am going to use oral amoxicillin and clavulonate, I actually prescribe it concurrently with SF 68. So now, does SF 68 correct the microbiome changes that are induced by clavulanic acid? It did not.
And so we could not, with the techniques used in this paper, show the probiotic correcting those, but we did show the probiotic had a clinical effect. And so further work's gonna need to now be done. With what is the probiotic doing, and most likely it's effect on the metabollo, not just effect on the different types of bacteria, but actually the metabolic profiles, and so that type of work will be ongoing in the future.
So this is an interesting one. Jackie Whittemore, the lead author on the end. Jackie was one of my PhD students, went on to Tennessee.
They did a nice job with the Nutriax symbiotic, where they gave it prior to clindamycin, and they were actually able to show lessen vomiting, lessen in appetence, but had no effect on the diarrhoea. And so again, we've got two good probiotics here, SF 68, product, the great probiotics, but I think these two papers really emphasise that probiotics are not the same. They're gonna have different effect on different hosts.
So we had a great effect on clavulonic acid diarrhoea, and then this symbiotic didn't do anything for the clindamycin diarrhoea. So you're gonna have to keep that in mind as you decide, what to keep on yourself. I really wanted to show you one of Dr.
Marks's paper, and here's this, Scott Weiss again. This paper will be redone here soon, but the trend that we all have in internal medicine, and I believe this is true in the UK as well as here, is we probably shouldn't be using antibiotics so early in these suspected bacterial diarrheas. I mean, yes, I do still see the tiles and responses of neuropathy and the German shepherd dogs, etc.
Etc. But when we have these suspected acute bacterial diarrheas right now I tend to reach for the appropriate. Veterinary diet that fits with either small bowel or large bowel or mixed, and then I actually do a probiotic rather than reaching for the antibiotic up front.
And in fact, especially for Campobbacter and salmonella, . We are very keen on only using antibiotics for Campylobacter and salmonella, if you know that you have sepsis, and that sepsis syndrome should be treated with systemic antibiotics, not oral antibiotics. And then if we do have some of these cases that an antibiotic is considered, to be potentially needed, Tylacine would probably be your best choice.
And, one of the Scandinavian papers did show that you probably only need about 5 mg per kg twice daily at the maximum. Some people even use once daily. So for the next little bit of this presentation, I'd like to chat with you a little bit about the immune modulatory effects of different veterinary probiotics currently on the market.
And this group of papers, I'll just show you two today that were sponsored by the company that makes DSL number 3, which is now marketed as the, the, . Biome group for dogs and and and also used in cats, even though labelled for dogs. This biome product that I showed you a little bit earlier in the talk, this one is a great combination of, of, of bacteria that have been shown to actually lessen the inflammation at the tissue level for, IBD dogs.
And it's, it was a nice study. The First one, and then the follow-up, that came out a little bit later was also quite good. And, and really documented that some of the microbium changes that are pro-inflammatory were actually lessened with this probiotic.
So if you had a case that you thought could be idiopathic inflammatory bowel disease, because they have published some work, it's actually not a bad choice. So again, a couple of good papers showing immune modulation, somewhat on the dampening side. There have been a number of atopic dermatitis papers now around the world.
This one's just a a review paper that you might be interested in reading, from a couple of years ago. There is active work going on that I can't share with you right now, but active work looking at probiotics that might come to market in the in the future. And bottom line is, It looks very promising that there are bacterium that could lessen the pruritus associated with atay.
And I personally find that to be quite, fantastic. I love drugs like Apaquel and now monoclonal antibodies. Certainly saved a lot of animals with bread.
But if I could actually lessen itching in dogs by feeding them, I would be OK with that. So you do your regular dietary hypersensitization trials, and then a probiotic as well. I think it's gonna be a great potential future for us.
So keep, keep your eyes open for those papers over the next 2 to 5 years. But now those two examples, this biome for IBD and probiotic bacteria for adiy control, those are kind of dampening the immune system. These work I'd like to share with you now or how about evidence that the probiotic could improve immune health or do anything specific.
So let's start with the paper that talked me into doing probiotic research. I, I ran into Jalilel Chris off at a meeting in Europe, and they said they had a puppy study coming out soon. And what I like to read it about a probiotic that Looked to have pretty strong immune modulatory properties.
And I said that'd be fantastic. They let me read the paper before it came out. And if you look carefully, they did the classic control group versus the supplemented dogs.
And over time, and in this case, it was numbers of weeks, they actually were able to show that the dogs fed inococcusheum strain SF 68. They actually did have evidence of non-specific immune turn on, in this case with increased IGA and faeces. If you look on this side, you'll see total IGA and total IgG and the serum with some pretty interesting responses in the serum for IGA.
And then if you look at these two charts, you'll actually see distemper virus specific IGA and IGD. These are vaccinated puppies, and as you can see, even with the IgG and IGA for a specific titer, again, in this case, came out to stemper virus, they were actually able to show separation between the controls and the supplemental. So that got me convinced that the B cell turn on looked pretty convincing with SF 68.
So nice paper, made me a little bit interested with some other studies with them. And then 2 years ago, we kind of circled back around this paper, but, you know, is it, is it a chance that there might have been some of these changes that might be kicking in a little bit earlier than 10 weeks, because that's when they started testing in the previous study. So we just finished a little study in beagles that will be combining with a study of Forta flora and pit bulls that I'll tell you about with demodex in a few minutes.
We thought that we would just supplement these young adult beagles with Fortiflora, and go ahead and do some of those same assays that had been done many years ago, but also with some new markers. And start testing them as early as 4 weeks after starting the supplementation. This paper has been presented in a in a ACBIM abstract.
And since the full manuscript is pending, I've decided not to show any charts today, but I can tell you that this work has shown both B and T cell immune modulation on the upside of immune stimulation as early as 4 weeks of supplementation. And, and why I thought that work was important was if I was gonna use sort of flora, say, for a chronic, trying to stimulate the immune system for a chronic UTI, which needs to be studied, or chronic demodex, etc. It'd be nice to know whether or not it kicked in earlier than 10 weeks.
Well, it does. So again, I'll look forward to your comments when the paper comes out that as early as 4 weeks. And I can send you the AVIM abstract if you'd like to see it before the paper comes out, just send me an email.
So what we did was then we said, OK, well, if it's kicking in as early as 4 weeks, and it does T helper cells, not just B cells, then a model that looks at dogs that are thought to have immune exhaustion might be a really good thing. We've already recently published a paper, with the support of Purina looking at pit bulls with and without generalised demodex. So that paper is in dermatology from last year.
But this paper was actually a clinical response paper. We wanted to see what would happen with these poor little doggies that have generalised nemodex like tulip came in looking like a little pink pig, Bart, dozer, he's pretty significant. That are keeping them from being adopted, of course, because of, of the way they looked.
And we were able to use a good demodex drug, in this case we used Advantage Multi. This was prior to the Bravecto study days. So we used Advantage Multi.
Some of the dogs were supplemented, others were not. And then we looked at mite kills, as well as our clinical response data. And the data suggests that supplementing generalised demodex dogs with an immune modulating probiotic had a beneficial effect.
Again, since this paper is in press, I can't share with you today on slides because this webinar can be viewed by others, but I did want to at least tease you with. Hopefully the manuscript review will be finished soon, and if you look at the befores and afters. We were pretty excited.
In fact, these dogs that were in the study, they've just come back for their second reunion. We adopt all of our animals after they've been successfully treated, and the resident that ran this project, Dr. Elena Contreras, he has actually had a couple of different, come back for the family reunion.
So very interesting. So I think you guys will be interested and will start considering using immune. Stimulating probiotics for management of chronic infectious diseases.
So again, look forward to sharing more data, when we can share after the manuscript acceptance, but I'd be glad to follow up with you if you have specific questions by email. But to close it out tonight, let me show you the other, and I think this is really the only other one, another paper showing that you can use SF 68 to manipulate the immune system on the positive side as an immune stimulant. And so this is one of my little herpes research kitties.
I'm sure you guys see them every day. This cat didn't need a probiotic as an immune stimulant. She was well in 3 to 5 days, so I'm not usually using a probiotic in the acute phase.
But what about those cats that just smoulder? You know, chronic rhinitis, chronic conjunctivitis. Could we potentially, by stimulating T helper cells, could we do anything to help those kitties?
And so one of the older papers, in fact, even prior to this publication, Doctor Beer, who was doing her PhD with me at the time, we actually did a study of healthy cats, feeding the meterococcus BSF 68, monitoring their wellness, as well as routine blood work, as well as immune function tests. And we were able to show that Enterococcus fe SF 68 is perfectly safe for cats at the dose that Purina was going to sell it at and increased proportions of T helper cells, greater in the supplemented cats than the placebo cats. So once we have that data in hand, I went back to them.
Gosh, it's hard to believe that was 11 years ago now. But I went back to them and said, you know, guys, if it really is a T cell stimulant. We should be able to use it to lessen recurrent herpes.
So this particular study, we actually had two groups of cats that had received the same dose of herpes in one of my other studies. We then housed those cats in two different rooms, and then one room was fed the probiotic. The other room was fed the placebo, which was the palatability enhancer, basically everything other than SF 68.
And then we wanted to give them a little bit of stress to then see which group would be more likely to have activated herpes virus, either by shedding or by clinical signs. And so how we induce the stress, normally our research cats that don't have to be caged, they live in group rooms, they have visual shields, multiple perches, multiple litter boxes, use the other boxes to hide in ping pong balls. They actually have a fairly good life in those rooms until they're adopted.
Well, they don't particularly like to be caged. And so what we would do then is we would shift from being in your gang room. To being in your same room, but now being housed in a cage, and then back to gang room.
So gang room caged, gang room caged, and that does disrupt a little bit of the pecking order issues, etc. In cats does lead to a little bit of stress. And in fact, we've been using that model now in other studies.
And so let me show you the microbiome work first, back to one of my earlier questions. Is there data suggesting that probiotics can impact the microbiome? Well, in this case, absolutely.
The diversity, the diversity was improved in the cats that were being fed for the flora during the times of stress compared to the placebo group. So we felt that meant a couple of things. One, that that the probiotic helped.
The stabilise the microbiome, but it also proved to us that the model was inducing some stress. And here's the clinical punchline for today. This is a little bit older paper, so I won't bore you with the whole study.
But when we compared the conjunctivitis scores over time, you know, between the supplementation stress period, we showed strong statistical differences between the kitties that were in the room being fed for the flora compared to the placebo room. We didn't show any difference with shedding in these cats. The stress model wasn't that potent, certainly not as potent as giving them steroids, but we can't give the healthy cat steroids in a Purina study, so we had to do the cage stress model.
So I hope to continue to do the field work which we're doing now. There's a nice cat in Madrid doing some work with, with chronic recurrent herpes signs. We have a couple of different study designs that we're considering for the future.
But when I look at what do we have available to us now to try to keep herpes cats that are prone to recurrence and remission, thinking things like lysine, thinking things like vamcyclovir. Well, lysine, you gotta give it as a dose. Acyclovir, you have to give it as a dose.
This particular product we can just feed them, and it tastes good, so even if they have low grade congestion, they often eat a little bit better because the fallibility enhancer tastes so good. So I think with this published paper, I can safely say, you would be crazy to try a month or 2 months of this probiotic as an immune stimulant to see if you could keep a rhinitis cat or a conjunctivitis cat in a stronger remission. Hope to someday do a study with mucositis as well.
So hopefully those will be studies we get to do in the future. So in summary, we have some pretty good probiotics out there now in your countries as well as mine. This one, the SF 68 strain of FS 68 that's in Fortaflora, has been widely studied in multiple species, not just the papers that I've shared with you today.
I personally think their data supports the use of this probiotic with acute diarrhoea, as well as chronic diarrhoea in dogs and cats. And hopefully we'll continue our work to see if supplementation might actually improve our GRD responses, maybe, managing other things like stomatitis, and I can't wait for you to see our four week data on the healthy beagles and in the pit bull study. Hopefully, the team will invite me back for other webinars in the future.
And for those of you that were not getting to see each other by face today, next time I see you at BSADA or London vet, please come by and say hello and follow up with me by email at mlain@ colostate.edu or through your Purina specialist. Thanks for listening to me drone on.
I hope my Oklahoma. Georgia, weird hybrid American accent accent was understandable. So Paul, are you still there with me?
I am indeed, thank you so much for that, Michael. It's a fantastic talk and the accent was just topping it off. It's wonderful.
OK, least tolerable, huh? We've got some really interesting questions coming in actually if you're OK to stay just for a couple, I know we're, we're at the 9 o'clock mark now. I'm fine, let's do it.
Wonderful, so there's lots of fantastic comments coming through and feedback, super fascinating talk. Thank you, thank you for an excellent webinar, which is great to see. So first question, quite an interesting one here, Nicola's asking, has there been much probiotic research with rabbits?
Obviously we know about the, the cats and dogs studies. Oh, thank you so much for that question, Nicholas. Yes, there, there's a little bit out there, but I've got to admit I've been, I've been kind of prejudiced and spent most of my time with the dog or cat.
So I, I would need to follow up with you offline from tonight. Just because I don't want to embarrass myself by misspeaking. But, I do have a colleague here at CSU that's quite interested in rabbits.
And if you want to catch up with me at that MAP and address, see if we can make a little progress, offline. Great stuff. Thank you, Michael.
. I got a question here from Han. He's asking, what's your take on Clostridium induced diarrhoea, as there are papers out there which show that Clostridium is part of the normal microbiome, and for example, the cat, which seems logical due to the amount of protein they eat. Yeah, thanks, Hans for that question.
I, I, I believe in Clostridium as a normal flora. Now I'm gonna talk about profreins, not difficile. The profreins is pretty clear to me that it's a normal flora, that if your microbiome or microbiota is disrupted in some way.
You know, stress associated diet change, another co-factor, you know, like another bacterium, like, Campybacter, you know, if you ate the bad piece of chicken. I do believe that we have plenty of data now that, that it can replicate and produce toxins that are specific to causing diarrhoea in small animals. So even though it's a flora, if it overgrows, then, then diarrhoea can be associated.
So I, you know, tonight trying to show 10 or 12 papers, I didn't delve into some of the other detailed parts of a couple of those manuscripts, but we have been following, different Clostridium, toxins in a lot of these different studies, seeing if we can make heads or tail, what role they were playing in the diarrhoea in these cases. And I've got to admit that they're so darn common, and the fact that we can, amplify a toxin DNA as well as measure the toxin proteins, it's really been hard to sort out. And so I'm gonna have to say right now with the data that we have in hand, I suspect that keeping that good diversity of the microbiome with the probiotic, is, is doing something specifically to Clostridium, but we don't have the data to say that strongly with the manuscript.
So it's a bit of a leap of faith to me that that's one of the ones that we're helping, especially in these stress type cases and shelter situation. A great question. Hopefully, we'll have some more specific data for you over time.
Yeah, absolutely, brilliant question, thank you, Han, I hope that's been useful for you and and great answer. Thank you as well, Mike. Let's have a look.
What else do we have here. We have a question. Do you recommend, in, having a gap between antibiotics and probiotics, for example, 12 hours between them.
Just thinking about antibiotics can kill probiotics if administered orally or at the same time. Yes, yes, that's a really great question as well. And you know, we struggled with that with the Clavamox study, for example, and Dr.
Whittemore, I know she struggled with that decision when she was doing the symbiotic trial with clindamycin because in those studies, the antibiotic, we know. Had a detrimental effect on the probiotic living. You know, metronidazole was a little bit easier when we did the metronidazole with SF 68 study, since we proved in culture that SF 68 was resistant to metronidazole, you know, we were able to go ahead and give them together.
So, so what's been debated widely in the human literature about giving a probiotic to lessen antibiotic side effects. It's, it's really, you can almost flip a coin with those that believe that giving the antibiotic first is a good idea versus giving the antibiotic after. So, so it's kind of split.
So when Emily Cross and I designed the Clavamox study, we ultimately just kind of Heed getting it before. And other, other great, questions like the one you're asking today and other meetings, you know, I thought it through. I mean, gosh, if I had to do a, a twice daily antibiotic like hyonic acid, maybe it'd be good if I could come home at at lunchtime and give the probiotic, you know, in the middle of the dose.
And all those things are great discussion that we just don't have data on. So for right now, if you, say you have probiotics to your favourite, mine happens to be SF 68, but, make sure you ask the company that you're per your probiotic is which of the routinely used antibiotics, inactivated. And if the answer is they don't know, and you probably want to go with a company like Purina that actually knows those kind of questions about their product.
And then if it's one that doesn't kill it, then I think you just give it at the same time, which makes it easier for the owner. And if it does kill it, you're gonna have to separate it by some interval. We just don't know what that optimal interval is and which to do first.
Those are just great questions that we'll have to sort out with continued research over the coming years. Yeah, absolutely, and it, it's worth mentioning that, you know, Purina have a huge global team, very knowledgeable team as well, so if you do have any questions, do contact your Purina reps. Just a question, with, with regards to the, metronidazole study.
What was the dosage, Xiao was asking in the, metronidazole and 4th flora diarrhoea study? Yeah, the Fortiflora, we use the, the label dose of Fortiflora, and we did that, for the entire length of the study. And then the metronidazole was, was for just the 7 days, and the shelter vet was in charge of the metronidazole dosing.
And so they would have done an approximate dose. They did not, did not officially giving, you know, they didn't liquify giving exact dose, and they were shooting in that, you know, 25 megs per gig, around, specific details in that paper, which way I can fire off to you by email attachment if you want to grab me after the lecture. Perfect, thank you very much, Michael.
Question here from Greg. Does 4 to Flora help atopic dogs, if they're under 1 year old, or should I recommend it for all atopic dogs? Ah, that's a great question, Greg.
I, unfortunately, we can't say anything right now about 4 to Flora and Atape. Yeah, I know fortiflora is an immune stimulating probiotic, and since it's a hydrolysate, it certainly won't hurt a food allergy animal, but I don't think it will hurt anybody that has inhalational allergies, but we don't have any information about that probiotic, actually being an adjunct for the treatment of atay. The, handful of papers that have been published so far have been different bacterium and the the kind of double secret stuff that we can't talk about today is with other bacterium and so right now I would say, you know, we just, we just don't know.
Would I be willing to on tape, speculate about what a chronic bacterial pyoderma, for example, potentially benefit? I am willing to speculate a little bit more on that, distribution of the question only because those demodex dogs, you know, we think that there's strong numerical differences in their clinical responses and things, because, you know, those pyoderma and Demodex dogs, you know, stimulating the immune system might be a good idea. We'll just have to wait and see on the adopy part.
OK, thank you for that answer. We've got a few questions coming in regarding probiotics and raw diets and diarrhoea. Now I'm sure we could have an entire webinar around this subject, but, but do you have any sort of overview thoughts on that, Mike?
Yes, yes, I think, basically what we need to do in the 21st century is anybody that tries to sell us something, ask them for data. You know, we, we need to support, the companies, drug companies, and our pet food, companies that actually fund research to prove their label claims, and that's few and far between on probiotics. So, don't be shy about asking.
That company to provide you some data, especially stability data and hopefully efficacy data, at least in some sort of study. And if those things can't be provided, you know, stick with the guys that are proving their stuff is good and and works for clinical problems that we care about. Yes, absolutely.
Evidence first. I think it's a good idea, and the institute, quite proud of Purina for starting the Institute. I'm glad to be part of it.
Absolutely. A really interesting question here. Have you noticed or seen a link between probiotics and musculoskeletal health, particularly in horses given their reliance on their guts?
Yes, yeah, that's really fascinating work and I, there are actually people, and I can just say people for now, working on that angle. And certainly folks like Arli Reynolds, working with probiotics and the sled dogs in Alaska. There's, there's some fascinating work out there, and I do believe that we'll see more of that in the future, just like effective microbiomema on things like brain health, and now we've got probiotics that lessen.
Lessen stress as you guys have been following probably with the Purina work. It's just amazing the impact that the the intestinal microbiome has on all body parts. Now we just have to figure out which bacterium, to work on and and so continued research will ongo hopefully the rest of our careers.
Yeah, absolutely. I know there's a few companies out there who are doing particularly the research on the horses has been published and I know there is some more research in the pipeline on the, the small animal side as well, so it'll be fascinating to see that when it comes out. We have a number of questions as well asking people, for the duration of, of usage of probiotics in different situations.
So diarrhoea or HP, Demodex, feline herpes virus. Yes, yes, those are always great questions. And, you know, with, with the, the small amount of data that we have, proving things and, and, and scientifically designed studies, it's a little bit hard to, to be definitive because we can usually only say what we actually did in this study.
But I am willing, since I am a practitioner and internist, to make a few general comments. One is that when I do an acute diarrhoea case, and or antibiotic diarrhoea, I generally do, you know, that two weeks of a probiotic, because one, you have to make sure that they tolerate the probiotic and you think it's helping. And if you're just gonna be on short-term antibiotics or, or, it was an acute non-specified diarrhoea, they, they may or may not need probiotic supplementation forever.
The other angle, though, the immune stimulation angle, you know, it kind of depends on the case. We still don't really understand, for example, why some kitties are so predisposed to chronic recurrent herpes, and then others who got the same darn dose of herpes, say, in the research. Study, never have clinical signs again their whole life.
You know, why some of us who are perfectly healthy otherwise still get stressed, cold sores, you know, and other people haven't had a cold sore since they were a kid. You know, we, we still don't understand that person to person animal to animal variation. And so what I think personally is a little bit lacking that hopefully we'll gather over the years is Should you take probiotics just for, say, general immune health?
You know, Jalil showed that very clearly that you maintain higher distemper titers if you feed a puppy cortiflora. However, their temer titers in the control group were high enough to present. Prevent distemper.
It wasn't that you needed to have the probiotic to keep you from getting distemper to make the vaccines work, but you could show an effect on immune health. And that's what's gonna be really fun for somebody to find, kind of like the great, you know, long-term diet studies, the work that's going on now with Morris Animal Foundation, with the golden retrievers, you know, trying to tease out some data that doing something that either stabilises your microbiome and Or, improves immune health by doing it every day for your entire life, is that gonna have a, you know, positive outcome like that? You're gonna live two years longer, like if you stay thin as a dog.
I just, we just don't have it. And so a lot of this has to be done on leap of faith, as well as what the, owners' beliefs are, you know, and those that believe in probiotics. I know for a fact that border Flora doesn't hurt anybody.
I've had herpes. Kitty's on it for, for months and months, months. And so, to, to work with an owner that's, that has ranked this Kool-Aid, that feels strongly probiotics are important, then using them for wellness, you know, for that person is fine.
To make that a general recommendation in my practise so far, you know, I'm still personally looking for a little bit more information. I'll fully admit that I take probiotics when I'm ill, not when I'm normal, personally. But that's again up to you, to still decide as we gather more data for you that, you know, convinces us should we be doing it or not.
So I don't want to say it doesn't work, but we also don't have data that says that it does. So for me, it tends to be short term or that course of time that I think is immune deficient or say an IBD case, inflammatory bowel disease is, is often for life if you can't remove the, the, food allergen. So that's where potentially an immune suppressive probiotic for long term might be indicated.
But it's really the wellness issue that I think I've struggled with the most. I certainly want to live longer. It would just be nice to have a little bit more data that it actually would work.
Absolutely. No, wonderful, thank you very much for that. Just a quick one, I, I, I think Libby's still online.
Libby, there's lots of questions coming in specifically about 4 to Flora. Is there somewhere that, is where's the best place for people to send their questions to there? It's probably they can send them directly to me.
So if you just email libby. Sheridan@purina. Nestle.com, and I'll be happy to answer them.
Excellent, thank you very much. And we will, we'll send out an email in the coming days, with that email address if you have any questions, then, Purina we'll get back to you. Thank you very much, Libby.
Some, still some fantastic comments coming in. Thank you, for such an informative talk. It's been really, positive, which is good to see.
We'll just finish with, one last question then, Mike. So, somebody is asking about the usage of prebiotics alongside probiotics. There's been some studies in elderly humans, with, showing it has an immune stimulation effect.
Do you know if there's any research in, in animals along this path? Oh, that's a great question. And the answer is absolutely yes.
That, that angle is something that a number of companies are interested in right now, and to me makes perfect sense. It'll now just be great to see, because obviously we have a number of different prebiotics and other additives that could be used, things like. Even as simple as pelium.
Yeah, we'll have to see how those pan out with, with actual clinical trials, but I agree with, the person asking the question that would make perfect sense, in theory, and now I just need some more work to prove that it's factual. Yes, yet again, more research, more data needed, which is, which is good. Excellent, we'll we'll end it there.
Thank you so much, Mike, for joining us and for presenting such a a wonderfully informative talk. We really appreciate you coming on for us. Absolutely, Paul, and I appreciate you picking out only the good comments to share with me.
It's entirely positive I can assure you that you're a kind man. And thank you so much, Purina as well. Yeah, thank you for Purina for sponsoring and making this all possible.
