Episode 164: Nutrition, Gut Health, and the Microbiome

Dr. Jason Gagné, a board-certified veterinary nutritionist at Purina, speaks about the mechanisms and impact of pre and probiotics on gut health, the immune system, and the microbiome.

Watch the webinar version of this podcast here.

Transcript

Nicole Engelman  00:04

Welcome to the Good Dog Pod. Join us every other Wednesday when we discuss all things dogs, from health and veterinary care, to training and behavior science, as well as the ins and outs of Good Dog and how our platform can help you successfully run your breeding program. Follow us and join Good Dog’s mission to build a better world for our dogs and the people who love them. Hi, everyone, and welcome back to another episode of The Good Dog pod where we discuss all things related to canine health. Research how Good Dog helps breeders run their breeding programs, and so much more. I'm Nicole, the breeder community Lead here at Good Dog and your host for this week's episode. Today, we're joined by our guest, Dr. Jason Gagné, a Board Certified veterinary nutritionist at Purina. He's joining our podcast to talk all about the mechanisms and impacts of pre and probiotics on gut health, the immune system and the microbiome as it relates to our dogs. So with that, I'll pass things over to Dr. Gagné, to bring us into the fascinating world of the microbiome.

Dr. Jason Gagné  01:07

Alrighty, well, thank you very much, really appreciate the opportunity to be here today and speak with you, Nicole. Michael, again, thank you for the invite. Great to be here. So without further ado, yes, I am a board certified veterinary nutritionist, you heard my bio there, I get to play a variety of roles within Purina and touch many different departments all the way from the r&d folks up front, all the way to the launching of products and training in Salesforce. So never any monotony in the day, which is what I love, and just occasionally get to give a presentation to some fine folks like yourselves. So again, in this presentation, we will be talking about nutrition, gut health, and the microbiome, and using manipulating modulating the GI microbiome to achieve optimal health. So typically, we think about certain areas of interests when it comes to gi conditions. Okay, so when dogs have gi conditions, in terms of nutrition, we begin to think about macronutrients such as protein, are they developing some sort of chronic enteropathy? Where they have a loose stool, or diarrhea, or even vomiting? Or both? are they developing IBD inflammatory bowel disease, and in those cases, since 70% of your immune system is in your gut, and the immune system is recognizing some sort of intact protein as that culprit for to trigger that enteropathy, that loose stool in that dog, we need to kind of go under the radar or fly under the radar of that immune system. And so proteins in some cases are visited, should they be novel proteins, you know, when you start to hear about this bison venison approach, Long gone are the days of fish meat novel or lamb Vietnam, which kind of gave birth to the idea of a hydrolyzed protein approach where you take an intact protein, you know, it's a big protein, and you break it down into small pieces, and therefore, it's highly digestible, even more digestible than your regular diet. But it also gives the same nutritional value. And it's the parent protein. Most recently, there is the ability to provide an elemental or amino acid based approach. So instead of working from the top down, you can work from the bottom and just stay there. And that's extremely readily absorbable and very effective for those chronic enteropathy patients. Carbohydrates are also looked at as the second macronutrients of interest in dogs with GI conditions. Sometimes we had to wonder, depending on what they are, should they be low, should they be high concentrations of them. So think about carbohydrates, as you know, you have your parent protein carbohydrate, underneath that is starch that we all know. But also fiber fiber is a type of carbohydrate, and within fibers, there are different ways of modulating the GI microbiome and we'll talk a little bit about fiber. And then thirdly, fat, everyone knows that fat is probably the hardest macronutrient and as the three of them to digest, and when a dog has a GI condition, we have to take a dietary history, we have to ask what have we been feeding and then lower that amount. Certain fats like MCT oils, which are known as medium chain triglycerides are more passively absorbed. So you can maintain palatability, you can maintain the energy density of that diet by inserting some MCT in there and still giving that pancreas and that GI system arrest and then omega three fatty acids from marine or plant algae sources that have been known to provide benefits. We typically think of fish oil as that source and that's an excellent source as well. But also all those omega three fatty acids have been helpful for being less inflammatory or D decreasing inflammation in many conditions like joints, brain, heart, skin, and so forth. But there's this fourth area that probably over the last 15 to 20 years, maybe that has started to be investigated, these bugs in the gut that we term, the GI microbiome, what are they doing in there, and who are they. And as time has gone on, we've been able to assess them and develop technology to assess exactly who they are. And because we've been able to do that, we've been able to assess their function as well. And because of that, from a pet nutrition, and myself as a nutritionist standpoint, I want to be able to modulate that and feed that so that it's good. And we can get those good bugs to proliferate, and then benefit the pet even more. So to put us all on the same playing field here. If you're not familiar with what the geo microbiome is, think of it as an ecosystem. It's kind of the environment that's in the gut. And it consists of fungi or KTI, protozoa and even viruses, and even all of those bacteria that we know and love, and they belong in there. And they're going to find balance as well, think of a seesaw if you will. That's imbalance. And then we're just again level setting here there are many micro biomes around the body, your skin has a microflora to it that is very distinct from your oral microflora, totally different environment, totally different bugs, and all in their own unique seesaw have a balance. That oral microflora is very distinct and different from the gut microflora and the GI microbiome, as we are talking in this presentation here, which starts in the stomach, and ends at the rectum. And as you start, in that stomach, you're dealing with a very harsh, acidic environment. So now many bugs live in that stomach juice, many 10^3 types or the fourth per gram of stomach juice. So you're talking about 100^1000 bugs. But as you go further and further along the GI tract into the small intestine, and then even into the large intestine, also known as the colon, you're talking about 10^1110 to 12. So billions upon trillions of bacteria, per gram of feces. It's fascinating, absolutely fascinating.

Dr. Jason Gagné  07:24

And then this is always one that people are kind of really taken aback by but approximately what percent of people wait Are these bugs, and then is about half. So half of the feces of a pen is these bugs can be gross, the sun can be exciting to others. But we begin to ask the question, what are they doing in there? Why are they there, and they actually have jobs to do? They work by themselves, but they also work in concert with each other as well. Providing energy balance 10 to 15% of your energy on a daily basis is derived from the byproducts of these books. So they're in there feeding on the fibers that we provide in a diet, producing these post biotics that we'll talk about known as short chain fatty acids that actually provide energy. Metabolism is another one we often think of, you hear about bile acids, bile acids, meaning your livers stored in your gallbladder, and they come out in are used as you digest fat. But as they're used and they digest fat, they undergo a process known as conjugation. So there's primary bile acids, they get used, then secondary bile acids, and they have to go back in that cycle. And to get through that cycle. There's actually one particular bug that plays a crucial role. It's actually known as Clostridium here and notice that conjugates it back so that it can be reused. And without that bug, or that bug is at a lower level. People have been known to develop bile acid diarrhea, which is bad, because it's been my daughter who rolls her eyes at anyone that says that.

Dr. Jason Gagné  09:11

But anyway, gut epithelial health is another one. We've known for decades that these bugs play a role in the health of the cells in the colon. And we'll talk about why in a little bit their immunologic activity, I mentioned that 70% of your immune system is in your gut. So these bugs are also interacting with an immune system. They're very intricately linked in the neuro behavioral development, we'll get into a little bit of that toward the end of this presentation, changes in the microbiome some sort of stress or comes along that causes the seesaw to go out of balance and in favor of the pathogenic or the what are thought to be the bad bacteria. It could cause a development of or contribute to the development of an inflammatory bowel disease, asthma, obesity, and at the bottom, I'll point out there Under neurodevelopmental anxiety to, again, we'll talk about that towards the end of this presentation. So here's your seesaw, you have the beneficial bacteria in balance with your potentially pathogenic or potentially harmful bacteria. And then as a stressor comes along within the intestine, there, you see all those pink intestinal cells along the way there in the schematic, you start to get more potentially pathogenic, the cells are kind of decreasing in size. And then there's even more potentially harmful bacteria, that then gives way to the development of the loose stool, and/or the diarrhea and even vomiting in some pets. So the stressors that a dog, or a cat even may undergo in life, life stage. And certainly this list is not exhaustive, you could probably think of six others on top of these six stressors that may occur in a dog's life. But life stage is one of them. They're coming to terms with their immune system, as we know, they're getting that mother's milk through the colostrum, they're picking up antibodies, they're, they're becoming more immune competent. And that's the whole reason for giving those vaccines starting at the eight weeks of age, while the mother's maternal antibodies drop in the vaccines begin to ramp up. Well, in terms of immune competence, that's the story there. But they're also coming to terms with their GI microbiome that is still developing, after they're born they get some of them from mom. But it needs to continue to develop. And while it's continuing to develop, there may be a loose stool. as they mature, and they go into the later stages of life as a senior, the gut epithelial health as the cells, the whole environment begins to change. You're not as spry as you used to be when you're younger. And those cells in the intestine don't regenerate as often as they used to. And that changes the environment, including changing the bacteria, too. So possibly these seniors can also benefit from some sort of microbiome modulations. The point there, infections are, that's obvious, you know, you have a viral infection, you have a bacterial infection, that's going to cause a disturbance in the microbiome, dietary change, possibly we didn't transition, as we were supposed to, and you went from a low fat diet to a high fat diet, you need a little help there to recover.

Dr. Jason Gagné  12:23

Broad spectrum antibiotics is a very, very hot topic within veterinary medicine at this point, taking a page out of the human medicine book, as veterinary medicine often does, we're beginning to understand and appreciate antimicrobial stewardship more. So instead of, you know, do I really need that antibiotic, and sometimes it is necessary to have an antibiotic and we should, but we need to think a little bit more judiciously about, are we contributing to an antimicrobial resistance? Do we really need that antibiotic? And if we do, maybe we complement it appropriately. I'll talk about a study where they complemented each other. And even since that study, maybe we need to start asking ourselves, do we need the antibiotic good old in some cases, maybe we just need a probiotic, or a synbiotic. And then traveling, environmental change, definitely big stressors for dogs, boarding kennelling, the shelter environment, and so on and so forth, could contribute, causing the development of that stress colitis when they get that large bowel diarrhea? So how does this all fit together? Well, you can see on this slide here, this endogenous flora, those endogenous being, you know, the bugs that belong that already are in your gut, they're already in there. And they're kind of symbiotic, they're benefiting each other with what are known as the intero sites, or the colonic sites, meaning the cells of the intestine or the cells of the colon. They're in this kind of symbiotic relationship benefiting each other. And then nutrition can come along through the use of fibers, particularly soluble fibers that are known as prebiotics. Probiotics are another approach. Those are the live bugs that you can supplement a pet's diet with. If they're put together in the same product, they're actually known as a synbiotic. And then colostrum colostrum we often think of as mother's milk. And it is, and it contains antibodies. But it is a little bit more than just passive transfer. And we'll talk briefly about that as well. But let's visit prebiotics first here. So as I mentioned before, you have carbohydrates as your parent, you have starch. And you know, fiber, I'm going to forget the starch for now, not relevant to this presentation anymore. Fiber certainly is. And prebiotics are soluble fibers that pass unchanged through the gut and go to the hind end into the colon with the large intestine. An example of this could be psyllium husk, and that's, you know, the main soluble fiber that's actually in the original Metamucil or console powder that you would find at Walmart. There are even some veterinary products like for the flora synbiotic AX, what happens with that psyllium husk, when it gets to the colon there is known as fermentation, think of the beneficial bacteria that are already in your colon. And they start to feed off of or ferment on those soluble fibers. And I will say this, they are actually selectively fed off by the beneficial bacteria. So, your beneficial bacteria tend to be bacteria that are known as Bifidobacterium, and lactobacillus and Anaru. caucus, those genus of species, and the bad bugs like Clostridium don't necessarily like them. But the good bugs do, the good bugs will feed off of them. And they'll be very happy, and they will proliferate. And it actually creates what's known as a microbial diversity, which is associated with increased health and wellness. So prebiotics are actually very good, long term, chronic usage of them. And what actually becomes of this, that's not the end of the story. So the prebiotic gets fed off by the good bacteria that are already in the colon. And then the byproduct of that interaction is what's known as a post biotic. And the type of post biotic we're talking about here, I have SCFA. In the bottom, you can see that same sort of short chain fatty acids. And those short chain fatty acids actually drop the pH of your colon just a little bit and make it a little bit more acidic, which may have bugs, actually don't like and will die off. But those short chain fatty acids are also the main energy source of the cells on the colon, which is kind of neat. So again, prebiotics have been around for a very long time, they have many benefits to them. And here are some of those benefits that a short chain fatty acid would provide. And what you're looking at in this picture here is kind of like a side view. If you were to take a cell and you cut it across this way, and you're looking inside it, what you're seeing here is a close up of the top of the cell, with this finger light projection here known as a villi. And what happens is this villi extends, it grows, and you're able to increase the surface area of which you're able to absorb nutrients. Short chain fatty acids are the primary energy source for the internet sites allowing you to absorb more water, more vitamins and minerals. And I've actually been known to help reduce inflammation and permeability God, and you don't want an increased permeability because that means that the cells aren't held tightly together. And you again, increasing permeability is a bad thing, because the cells will break apart and you'll get a leaky gut. So now moving into colostrum, not just for passive transfer. Again, we know that for the neonates, pediatrics, absolutely the first 24 to 72 hours, we need mother's milk, we need to get those antibodies, and defensins and transparent etc. But keep in mind, as I mentioned before the intestinal tract is the largest immune organ of the body 70% of the immune system is in there.

Dr. Jason Gagné  18:14

Even as an adult supplementing colostrum, which contains these antibodies, these Halo wise, those can be absorbed, they can be internalized by those immune cells. And what happens there is one of two things. The first thing is that this immune cell absorbs that antibody and says, Hmm, this is very interesting, I want to let the rest of the regional area here know what's going on, they become activated, and they begin to send signals out to the rest of your system known as cytokines. But those signals go out and the rest of the immune system says, oh, okay, I'm going to make some antibodies here towards that, or immunoglobulins, and that's known as IgG. So in other words, by supplementing with colostrum, you are priming your systemic immune system. Additionally, the lymphocyte doesn't necessarily need to send the signals systemically. It's also looking at what it's internalized in and of itself and saying, this is interesting right here, I'm going to produce an antibody locally for the GI tract known as IGA. And therefore, you get a systemic and a local priming of the immune system. And this is important, because no matter when what life stage, whether it's a puppy, a mature senior dog, you're priming that immune system to protect against pathogens, and this has been shown to be very useful, and in studies has actually been shown to increase their titer levels and be defensive against disease conditions. But as applied to the GI microbiome, there was a study that was done up in Alaska with 24 Alaskan sled dogs. It's an exercise stress model. And if you're not familiar with sled dogs, they are a wonderful stress colitis model, because the training and the race that they go through is a stressor that can cause loose stool. So in this study, there were two groups. One is being fed a test diet. The other group is being fed the test diet with the bovine colostrum. So the only variable there is the bovine colostrum. And any changes must be due to that bovine colostrum, because everybody's in the same environment as well and eating the same diet. This study went on from July of one year into April the next year, so 40 weeks long, very long study, and then looked at the GR microbiome, pre and post a stress event so pre and post the training BV. And what was found was the dogs that were being fed just the test diet in the gray, they were only able to maintain the stability of microflora from pre-stressor to poachers to the tune of 46%. Whereas the classroom group was able to stabilize their microflora to the tune of 82%. They say, Well, why is this important? It's important, because we want to have a stability of that microflora, we want to keep that seesaw in balance, because if it goes in the direction of the pathogenic bacteria, because of all the stressors I mentioned earlier, the kenneling, the boarding, what infection, whatever that may be, in this case, it's a race for sled dogs, but it's mimicking other stressors in life, we want them to be able to stabilize that microflora, rather than going out of whack or known officially as a dysbiosis and giving way to a loose stool. So colostrum was able to stabilize that and it's very beneficial towards feeding those good books. I'm going to move into probiotics at this point. So just to review here, the difference between a pre and a probiotic is the prebiotic is the food for the beneficial or good bacteria that are already in your colon, they go into the colon, they feed those bugs, and you get more beneficial bacteria. Wonderful. Probiotics, on the other hand, are beneficial bacteria. were supplementing the dog's diet with a probiotic, for example, they go into the colon, and then they give way to more beneficial bacteria in the colon, as well. And both of these are different approaches to creating a healthier intestinal environment, the way probiotics are working, they are going to go in, and they are going to bind to those intestinal cells for the benefit of those intestinal cells. And because they are binding, they create a physical barrier to the pathogen. And if the pathogen can't bind, it can die off. Another way that they're working is that when they do bind to the cells of the colon, they are competing for nutrients, the food substances that are passing through the colon, and they're competing against the pathogens. So if the probiotics are feeding off of those nutrients, the pathogens aren't and will starve and die is another mechanism. And then lastly, probiotics actually have the ability, certain ones do have the ability to interact with your immune system, as I mentioned before, and when they do that, they can actually activate the immune system to produce what are known as antimicrobial substances, or immunoglobulins, or antibodies that can then kill the pathogens as well. So multiple ways of acting here that probiotics are beneficial. The characteristics of a good probiotic, I know it sounds obvious, should be safe, non invasive, non carcinogenic and non pathogenic, they should be able to survive the GI tract. Many probiotics actually cannot remember that the stomach is a harsh environment of acid and many probiotics actually will die in the stomach and have no effect. Probiotics should be able to get through the stomach. And then when they get to the intestinal cells, they should be able to adhere and bind to them and do their actions like affecting pathogen growth and blocking attachment of pathogens. And then genius of probiotics that have typically been used are Enterococcus, lactobacillus, and Bifidobacterium. And we'll talk about them in a second too. I provide this slide here because I want to provide a little bit of perspective. There are different regulatory systems and therefore the FDA in the states acts in different ways. The FDA is very tight on drugs. I think we could all agree on that. And I think we're all happy about that drugs, as the slide says, intended for diagnosis, cure, mitigation treatment or prevention of disease, and they have a very long pipeline, but the FDA is very tightly linked with dietary supplements. As you can read here on the right, it has a very circular definition. Okay, it's a product we're taking by mouth that's intended to supplement the diet. So a supplement is intended to supplement. Okay. There is actually no FDA approval necessary. First dietary supplements, but the FDA does want to know that they're being put on the market. But they're not as hands on as they are with, let's say, pet foods, pet therapeutic foods. Supplements is a little bit of kind of a wild wild west territory. And this is where I'm kind of pointing us to to say, we need to be a little bit more informed about the probiotic supplement that you're choosing and understanding who you're recommending, who you're using, and why you're choosing. So I always say that you should be using a supplement that has been studied in trials in the target species of use. So a dog probiotic for a dog that's been shown to be efficacious for the condition you're talking about. So if we're talking about diarrhea, for example, that was able to alleviate diarrhea or infirm of that stool. In fact, there's a gentleman if you're not familiar with him, his name is Scott Weitz. He's at the University of Guelph. And he published a study in 2011, where he pulled 25 products over the counter for both dogs and cats and asked the questions do you have the amount of live bacteria you say you have? And are you able to label your product correctly, and he would be the person to do this, because he's an internist. But he's also a microbiologist as well. And of these 25, what he found was that only two of these 25 products were able to label their products accurately, which is kind of sad if you think about it. But when he cultured them, and actually asked the question, do you have the amount you say you do on your label? It's one thing to say, I'm putting in, you know, a million, a billion a trillion bacteria. But after it's produced, do you have the trillion bacteria, and he found that, again, only 225, were able to label the product correctly, and actually have viable or live bacterial colonies. So there's a lot of products out there where people are buying dead bacteria, that's my point.

Dr. Jason Gagné  26:58

So again, know who you're working with, and understand the research that went into the development of that probiotic and be choosing those probiotics. Another one that I do want to mention is that there's a lot of talk out there about, does the strain of the bacteria of these probiotics actually matter. And it really does. So you can have enterococcus faecium. And then you can enterococcus faecium SF68. Think of a bug's name, as your own name, there's a first, middle and last name, you don't really know who you're dealing with, until you know all three names. So it's one thing you know, my name is Jason William Gagné. But it's one thing to say I know Jason William, many more Jason Williams around there are more Jason Williams, then there are Jason William Gagnés. So you really should know all three names, because what happens here is that the benefits could change just on the strain alone. So for example, not going to get into giving the full name here, but you can see that they're both lactobacillus reuteri, but they have different strain names. And you could see that they have completely opposite effects. So it's important to understand exactly who you're dealing with. It's not enough in this case to say I have lactobacillus reuteri, right? Yeah, what strain and many products are not very efficacious or very forthcoming that who that strain is. So looking for the strain name is my point there. And then we have a multi strain probiotic. And a lot of people think, well, you know, I have a single strain of enterococcus faecium SF68, okay, fine. But what if I put the six other strains along with it? Just because you put seven, what are termed beneficial strains together doesn't mean that it's more efficacious. I often think about multi strain bacteria, as kind of like, children in a sandbox, you know, we all say we have good kids, right? So you have a good kid, I have a good kid, the next person is a good kid. We all have good kids unto themselves, but eventually take all these good kids, and you put them in a sandbox and somebody isn't getting along. So does the bacteria that's on the left there. Does that produce something once it feeds off of the good fibers, right?

Dr. Jason Gagné  29:20

That inhibits the growth of that blue wire on the right, or does the blue wire actually go head to head with the orange rod right next to it when it's in the gut? Can't really say that you have a multi strain product that's beneficial unless you've actually studied each strain individually, showing the efficacy of each frame. And then putting them together actually is a one and one equals three, if you will. So that's the idea behind a multi strain probiotic. And I will say there were very, very few strains of bacteria that have been studied in veterinary medicine for the benefits of dogs. That puts all of their strengths together. Has not been studied, I have yet to meet the multi strain probiotic that is actually done. To me, knowing the string you're working with, that has been researched in the target species of use and have studies that back that is the most important thing. So let's get into a few studies looking at the benefits of probiotics. So I know we're talking about dogs. But this is a study demonstrating the benefits towards diarrhea in kittens. This is a year long study. And this is a study where kittens were in a shelter environment. So eight weeks of age up to a year of age. And so they're, you know, two months to begin with three months into the study. So five months of age, they again, all exposed to the same environmental variables all eating the same diet, one group is getting a placebo, the other group is getting the actual probiotic. And at five months of age, there is a protozoa, Tritrichomonas foetust, is actually commonly known as tri-tric, goes through the shelter, it happens. And the control group develops diarrhea to the incidence of 60%. The group getting the SF 68, the probiotic, only about 9%, diarrhea. So again, quite preventative, the days with diarrhea in that control group of that 60% in the control group, about 45 days of diarrhea that needed to be given an antibiotic. But the probiotic group, only about 18 days that they needed an antibiotic. So this is really the closest you're going to come to say, Yeah, you know what, if I need to take my dog candling boarding sheltering them traveling somewhere, or whatever other scenario, you may think of where they may be exposed to a stressor, maybe you want to get a probiotic on board, a week or so ahead of time. I usually tell folks seven to 10 days, acute stress diarrhea and dogs, another Alaskan sled dog study, 26 dogs, two groups of 13 each horse have seven days where they're all exposed to the same environmental variables. They're all eating the same diet. And again, the difference here being one group gets a placebo, one group gets the SF 68 probiotic. And we're going to look at the fecal quality in terms of consistency. The results of this study are that the placebo group over the seven day period is able to firm up to a normal stool to the tune of just shy of 40%. Soft stools are 26 and watery stools of 34. When we compare that to the probiotic group, the probiotic group is able to firm up to the tune of 65% of normal stools, and only 13% watery stools. And what's interesting is while the probiotic hand over fist does clinically insignificant statistically significantly better. The rate of improvement in the probiotic group was quicker as well. So they were able to get onto the road of recovery faster in this study.

Dr. Jason Gagné  33:03

Here's the study I was talking about with antibiotics. So this is a shelter study that was done with Dr. Michael Lapin and Colorado State University. And in a shelter environment, you know, dogs will develop diarrhea metronidazole Flagyl is a common antibiotic in veterinary medicine. We all know it and wanted to show the efficacy of how well does metronidazole do alone, which was four and a half days approximately here as you can see, and firming up the stool versus metronidazole plus, in our Enterococcus faecium SF 68 that dropped them to only 2.8 days until recovery, statistically, but more importantly, in this study, clinically significant here. I think we can all agree that, you know, well, some people may say well, we're still over 20 days. You know what, that's a difference of a day and a half and if you're the one that's picking up that diarrhea that is definitely significant for you. So since this study has been done, folks have looked at just utilizing enterococcus faecium SF68 alone and showing that you're dealing with still in a two to three day window sometimes even shorter for recovery just with a probiotic alone. And then this is a study that was looking at the immune function and showing the ability of SF 60 to modulate the immune system in shelter cats here. As we know, cats, 95 to 99% of them have feline herpes virus or FHV. One I just kind of ubiquitous out there. And one of the clinical manifestations of feline herpes virus one is pinkeye conjunctivitis during this study, the control group, about 29% of them develop conjunctivitis, whereas those that were on SF 68, only half of those so but 14 and a half percent developed it so again, really just showing the efficacy driving home the point here that probiotics can modulate the immune system for the benefit. And since this study, Dr. Lapin has done a number of studies with me and says they've been both dogs and cats, and actually has shown the benefits of recovery from a generalized demodicosis in dogs, a very nice warming study for adopting shelter pets, has also looked into why this is occurring and has dug into trying to figure out the exact mechanism of how the probiotic is interacting with the immune system. So fascinating work there that he's done. Now we're going to move into, we've talked about prebiotics, we've talked about probiotics, but if you put them both together, in one that is known as a symbiotic, so they should be acting in harmony there. And when you do that, you need to really revisit which prebiotic am I going to put because there's many soluble fibers out there. And there has to be a rhyme or reason for why you're choosing which prebiotic to put together with which provider. So in terms of GI, as I just shared, enterococcus faecium SF68 has been very beneficial. So that is kind of a no brainer. But psyllium, again, that psyllium husk is very beneficial, because it has different characteristics. It is a soluble fiber, it's viscous, too. So what happens is, as it goes into the stomach, it's going to absorb some water to help bulk up school, you're trying to bulk up, causing fecal formation instead of a watery stool. And it's also slowly fermentable, as well, meaning that it's bulking up the stool in one sense, but when it gets to the colon, the good bugs can still feed off of it and improve that microbial diversity that I mentioned earlier. So kind of hand in glove.

Dr. Jason Gagné  36:43

Going into the development of such a product, it has been challenging at times, and has actually been very rewarding in the end. So as you can see here in this in vitro study, meaning taking fresh feces from dogs, pooling them together, and then subjecting them to psyllium alone, or psyllium, plus the probiotic to actually show that the combination is better than just the psyllium alone. On the bottom left, the psyllium actually did slightly better than the fauna flora, is a keen eye for lactobacillus. But when you move over just writing it, the bifidobacteria, again, lactobacillus bifidobacteria, both good books that you want to increase, the bifidobacteria increase significantly through use of synbiotic. And then the real clincher is that, as I mentioned before, you want to drop the pH of your colon slightly, because that helps kill off or create this inhospitable environment for those bad bugs. And synbiotic were able to achieve that better than selling him alone. So from here, taking these findings, and others that I would love to share with you, but we just don't have enough time in the day, moving forward and saying, Okay, let's do an in vivo study, with 24 Puppies, 12 in each group, the synbiotic versus a placebo, nine week long study, they're starting off at eight weeks of age. And we're going to look at different ways to assess the microbiome. As I mentioned at the beginning of this presentation, there's different ways to assess the microbiome. And it's exciting that we're able to do that and technology increases. But if you're the one that's making products you have to keep up with. So we continue to keep up with the latest and greatest technology with our products as well. And in this case, utilizing the old method of qPCR, we were able to increase what's known as the Cali bacterium, more than just the placebo. And the reason why you want to increase what's known as V Kelly bacterium is because decreased concentrations of that are associated with dogs that have inflammatory bowel disease. Another way of looking at the microbiome is through relative abundance, which is known as 16 S. And the ways of doing that were shown that we were able to increase the families of good bacteria as well through the synbiotic. And then the third way is looking at microbial diversity. And that's the newest way of assessing the microbiome, alpha and beta diversity and that alpha is that long rectangular box there in the middle, that you see where the test or the symbiotic and blue is able to increase higher than those than the red of the placebo. So meaning we're able to increase the overall abundance of the overall bacteria higher in the symbiotic group. But what's more important is to pair it with what's termed a beta diversity on the right in blue or symbiotic oval is tighter. So it's more of a cluster of good bacteria that are increasing in those dogs. The dogs are more likely to have beneficial bacteria. So that is the definition of increasing microbial diversity, again, associated with increased health and wellness in a chronic sense, which is great. And then lastly, I just want to talk about anxiety, we did talk about neurobehavioral development here. 29% of dogs suffer from at least one anxiety issue, but to put the 29% into a number, that's about 23 million dogs in the US. So there's a ton of dogs there that have at least one anxiety or fear issue. Body language is something that we need to get more in touch with and recognize that and anxiety does manifest in different ways. Whether it be separation anxiety, we leave the dog becomes destructive, or the dog urinates or defecates around the house. Noise phobias, most fireworks, and then fear based behavior too. So again, different ways that anxiety can manifest in dogs, signs of anxiety, you could see here, the vocalizing, the barking, the pacing, even spinning, compulsive licking compulsive behaviors as well, that fear based behavior. There are many solutions to anxiety, which we cannot forget behavioral modification that should be done employed, always positive reinforcement in dogs is wonderful. Multimodal environmental modification or MIMO is meant more for cats. There's pharmaceuticals old, tried and true of Prozac, Xanax, Clomipramine, so on and so forth, that may or may not do a decent job. But owners really don't like the perception of drugging their pet and the side effects that come along with them. And lastly, what is the cost of some of these drugs. And that's really giving rise to the supplement and pheromone therapy category here, which again, those two have their percentages of efficacy. And then lastly, wearables. If you're not familiar with the thundershirt, it's like giving a hug, kind of like a little bit of a snug shirt on the dogs as well. We had Purina look at enterococcus faecium SF68, since we knew it would be good for gut health and Gianna comfort. But was it good for stress? We actually did look at this, just because you know, is there a nutritional solution to anxiety, and it did actually work for stress, but it wasn't clinically significant. What was interesting was that Nestle Health Sciences had done a study of humans where they self-reported and said, we feel that we're less anxious with this bug known as Bifidobacterium, longum, BI999. And you see that Bifidobacterium is shaped like a Y, because they actually are shaped like a Y under the microscope. And what somebody had done, actually a gentleman that studies gastroenterology in rodents in McMaster University in Canada, has looked at anxious behaviors in mice who and he has a predilection towards GI. So he's looking at the gut brain axis. And he actually found that supplementing mice with Bl999 actually reduced the anxious behavior of these minds and cleared up their infectious colitis, you'll begin to wonder how that works. Well, anxious behavior can actually transfer through gut microbes. And the way this works bear with me here is we have an anxious mouse that we can pull out a sample of gut microbes and put them in this blue mouse here that happy go lucky mouse. And a happy go lucky mouse will become an anxious mouse. You follow this up and say you have obese, anxious mouse, take a sample of the gut microbes, put them in ideal weight, happy go lucky. And happy go lucky mantle's ideal weight becomes ideal weight, anxious mouse and say, Well, why did you become obese? I don't know. Maybe he's stressed he's over time he becomes obese. That's not the point of the slide. The point of the slide is you could transfer anxious behavior through the gut microbes. And the way this is working, is through this schematic here that some folks have figured out part of the mechanism of action, no one's figured out the entire mechanism of action, but we do know much of it. And right here at the bottom where it says enteric microbiota, that's the blue Y's would be that BI999, that Bifidobacterium longum. That goes into your gut, produces some sort of metabolite no one knows what that is, that acts as what's known as a neurotransmitter, meaning it can send a signal to the nervous system to this vagus nerve, which is a cranial nerve. So it’s brain to gut and gut to brain and it's bi directional, and that is how this mechanism works. So this is the way that these bugs can help decrease anxious dogs.

Dr. Jason Gagné  44:28

So in a study of 24, anxious Labrador Retrievers, all fed the same diet, complete balanced diet 12 dogs in each group, one group is fed placebo, the other group is fed the B.longum, the bl999, for six weeks. Every day they're looking at barking, jumping, spinning pacing, and at the end of six weeks is a formal anxiety test. But then this three week washout period gives enough time for you know, receiving nothing and knowing that a probiotic needs usually provides an extended two to three days at most, so three weeks is plenty. And then it's a crossover study. So if you got placebo first now you get the veal 99 and second half. And if you got veal nine and nine, then you get placebo. So the dogs act as a rule control. We know how they are on the BMI. Now we know how they are on placebo. And we can do statistics based on that. And again, the same measures of barking, jumping, spinning pacing in the second half performance anxiety tested the very act. And you can see the day to day behaviors. On the left here, as I just mentioned, barking, jumping, spinning pacing, a formerly anxiety test where the dogs are brought to a room where there's some classical music playing that then is turned off. So how do they react to the silence? A startling sound like champions equal or elephant poll happens? How do they react to a novel object like a balloon comes out of the drop ceiling? A stranger, you know, dressed like a handyman comes into the room, and then the handyman leaves. So how do they react to that? And the interesting part about this study was that it was actually peer physiologic activity with those behavioral measures, no study, up until this point had done that. So the holter monitor was measuring their cardiac activity, and taking swabs of the saliva to measure their cortisol too. So again, really bolstering the findings of both of them by heavy behavioral and physiologic parameters. And the results of this study show that the treatment, or the Bl999 group, had much significantly reduced and clinically significance to reducing all of those parameters or controlling spending pacing compared to when the dogs were in control. And then their salivary cortisol also decreased in a play yard activity, but also at the end of each of the phases, when they got the Bl999. So really, really cool. The heart rate was significantly decreased. That was measured on that holter monitor. And in each of those measurements, in the formal anxiety test, I mentioned, the music, the silence, and so forth, significantly decreased heart rate over the placebo group, which is phenomenal. So the gist here was that problem behaviors are decreasing stress responses, decreasing heart rate variability, which is not as intuitive increase, but that's a good thing to increase heart rate variability, you don't want to be so staccato where it's kind of like a fight or flight mode, where boom, boom, boom, you know, just slight variations in your heart rate variability means you're more calm. And this all leads to more positive changes in emotional states dogs. So I'll leave you off with this, once again, where nutrition is really at the forefront of manipulating modulating this gut microbiome for the benefit of these dogs. And at this point, I'll take any questions.

Mikel Delgado, PhD  47:37

Excellent. Thank you so much, Dr. Gone. Yeah, that was fantastic. I have questions. We got lots of questions from our audience. And I know we're getting a little close to the time we'd agreed on. Do you have a few minutes to answer some questions?

Dr. Jason Gagné  47:48

Sorry, Mikel, went on mute there. And I apologize. I did go a little bit longer than I expected. But I appreciate you all bearing with me. I do have a few minutes.

Mikel Delgado, PhD  47:55

Great. Excellent. So just to let all our attendees know we are going to focus on questions about probiotics, prebiotics, and the microbiome. So we probably will not get too specific, like dietary or nutrition questions. But we'll start with the macrobiotics questions and see how we do. But first of all, we have a question. We are hearing more and more about gut health as it pertains to yeasty ears, and that we should be giving a probiotic to solve this problem. Do you have anything to say about the interrelationship between gut health and skin? And should probiotics help with these other issues?

Dr. Jason Gagné  48:27

I actually do have a lot to say about that. But I was spared. So there is a skin microbiome that is separate from the whole germinal logic and actually, within that dermatology area, the ear is completely different so it really depends why what is the root cause of the ear issue? And is that related more to what's known as atopy environmental allergies? Or is it related even to a food allergy, which is manifesting food allergies in these dogs? So manipulating through the gut can be beneficial towards atopy. And also towards food allergies. In the future. I can say I don't think we know enough yet. We don't know what we don't know there. And that really has to be researched and studied. Anything going on right now that people have been saying this probiotic is good for years, I feel is a little cart before the horse.

Mikel Delgado, PhD  49:15

Okay, premature. Okay, great. We did get some questions, because you mentioned there was a study that found that two products delivered what they promised. And so I was curious, well, and other people are curious, like how do they choose a probiotic product at this stage? How can they discern between a good one and a bad one, you can make a specific pitch for anything.

Dr. Jason Gagné  49:36

I would say ask the source where you're getting it from. Make sure that it's been studied in the target species of use as your veterinarian if you want to. That would probably be the more reliable source versus the person at the pet store. But it needs to spell out the name as I mentioned, like Enterococcus faecium SF 68 on the label. It should have an expiration date. It should have a guaranteed amount and of each strain, if you're going to have to use a multi strain, which again, I have my doubts about maybe in the future multi strain, but again that has to be studied.

Mikel Delgado, PhD  50:11

Okay, great. And we did get a question about whether or not multi strain is preferable and I know you addressed that in your talk and you just use it now. So the answer is no. We got a question about bacillus. Some probiotics contain species of bacillus, I didn't think bacillus was a natural member of the gut microbiota. What does it do?

Dr. Jason Gagné  50:29

Bacillus, particularly Bacillus coagulans, is one that's used. And whatever strain after that may be, but no, it is not. It's a yeast. It is a little bit more hardy and processing for manufacturers. And it can shift its shape to survive extrusion or retort systems in manufacturing. But it does work. It has benefits. I would say, if it's been studied, it may not be endogenous, it may not be inherent to a dog. But if it's been studied to have benefits, and that dog, and there's research behind that, to show those benefits, and nothing wrong with that, in my opinion.

Mikel Delgado, PhD  51:02

Okay, someone just asked a question I also had, which is do these products need to be refrigerated? Should that be a factor when you're purchasing them?

Dr. Jason Gagné  51:09

Only if you care about that?

Mikel Delgado, PhD  51:10

Okay, so what is the effect on

Dr. Jason Gagné  51:12

I mean, there are some out there that do say they need to be refrigerated. I would not refrigerate them. If it does not say to refrigerate. No need to refrigerate something that doesn't call for it.

Mikel Delgado, PhD  51:21

Okay, great. What about the effects of giving probiotics to a pregnant or lactating bitch? Does that benefit her puppies?

Dr. Jason Gagné  51:29

People have been curious about whether there have been some small quaternions during parturition. It does seem to show benefits. I don't know if products are actually labeled for that reason, though. But it could be beneficial.

Mikel Delgado, PhD  51:44

Okay, so would you recommend probiotics or prebiotics for pregnant dogs or?

51:48

Definitely prebiotics? Probiotics, again, I don't know of an official, there have been small studies, but nothing actually published on that.

Mikel Delgado, PhD  51:56

Okay, great. Here's one. While we use probiotics and prebiotics to build the immune system, are we compromising reproduction? There was a question about a drop in pH. And I think you were talking about pH in the gut, right?

Dr. Jason Gagné  52:08

In the colon, yeah.

Mikel Delgado, PhD  52:09

Is that going to affect the vaginal pH at all? Where there might be concerns about getting a dog pregnant?

Dr. Jason Gagné  52:14

No, that hasn't been shown. And again, it's not a major drop, and like, you know, seven to a six or five or anything like that. We're talking, you know, like, a 0.1 difference or a 0.2 and that's what you're trying to achieve. And I'm trying to achieve big swings.

Mikel Delgado, PhD  52:28

Okay.

Dr. Jason Gagné  52:28

Very small that does not have an effect on reproduction.

Mikel Delgado, PhD  52:31

Great. Okay. Another question. Would it be redundant to purchase probiotic supplements, if you are already feeding a food that is fortified with pre and probiotics?

Dr. Jason Gagné  52:41

It may be and also remember, it depends what you're after. So remember, which different strains do different things. So if you are feeding a food that has prebiotics, all the power to you, I think that's wonderful if you're feeding a food that has probiotics in it, what is that strain? And what are the known benefits of that strain? So again, I just shared with you one probiotic that does gut health, and I showed another one that does anxiety. So it depends on what benefits you're looking to achieve. So depends on what you're trying to achieve.

Mikel Delgado, PhD  53:21

Okay, excellent. And that kind of relates to this question, which is just if a dog has consistently loose stool, parasites, giardia and coccidia have repeatedly been ruled out. So would you recommend a probiotic or prebiotic? You know, I know you can't make a specific treatment plan for a dog. But would you say that those could help a dog who has chronic loose stool?

Dr. Jason Gagné  53:39

Yeah, I would say I can't come up with a treatment plan from that. But yes, I mean, like, nothing wrong with trying a probiotic that's known to be beneficial towards loose stool in that instance.

Mikel Delgado, PhD  53:51

Okay. You mentioned that, you know, stress impacts pets as they age, would there be any reason to look at different strains of beneficial bacteria based on a dog's age or breed?

Dr. Jason Gagné  54:02

Yeah, there wouldn't be. So again, we don't know. We don't know. No one's ever really characterized the GM microbiome throughout the lifespan of a dog. But there is work being done there to actually get more and more specific. Well, I think in 10 years from now, we're going to see a lot more specific probiotics.

Mikel Delgado, PhD  54:21

Okay, great. So, when starting puppies on food, is it too soon to add Pro and prebiotics?

Dr. Jason Gagné  54:29

You know, the reason I say about the partiration, the birth one is like, we don't really know only small studies that have never been published up and down there. But we do know starting at eight weeks of age, that probiotics are safe.. So nothing wrong with starting there. And I would be feeding prebiotics in my pets food throughout life.

Mikel Delgado, PhD  54:49

Great advice. Okay, well, I'm going to give you the rest of your day back. I appreciate you staying longer to answer questions. Thank you so much for this excellent talk. I think it was super helpful. To a lot of us, and I really appreciate your time.

Dr. Jason Gagné  55:03

Well, thank you very much. I hope it was helpful. And again, I really appreciate the opportunity. Awesome.

Nicole Engleman  55:07

Thank you all for joining. I echo what everyone else is saying. I love this webinar, I learned so much so to everyone who joined if you like this and you like learning about canine education and health, please keep an eye out for future webinars and Facebook Lives. And podcasts. We offer a ton on topics like this and others related to Canine health. So definitely follow along at good breeder center on Facebook, to keep updates on all of these things because we always have so much going on. So that wraps up this week's episode of The Good Dog pod. We hope you learned a ton about the microbiome. I know I did. And we hope that this will be a helpful resource for you, your programs and of course your dogs. Thank you again for tuning in. And we'll see you right back here on May 29 For our next episode. Thank you for listening to the Good Dog Pod. We'll be back in two weeks with another episode so be sure to subscribe to the Good Dog pod on your favorite podcast platform.