We are back at the Real Science Exchange, and this week Dr. Barry Bradford and Dr. Turner Swartz, both from Michigan State University, join us. This week the pub table discussion is focused on The Evolving Field of Nutritional Immunology. The conversation at The Exchange kicked off discussing that you can’t ignore the immune system and its integral involvement in day-to-day physiology.
Guests: Dr. Barry Bradford, Michigan State University
Dr. Turner Swartz, Michigan State University
We are back at the Real Science Exchange, and this week Dr. Barry Bradford and Dr. Turner Swartz, both from Michigan State University, join us. This week the pub table discussion is focused on The Evolving Field of Nutritional Immunology.
Dr. Barry Bradford presented as part of the Real Science lecture series. His presentation, “Feeding the Immunity Defenders; The Evolving Field of Nutritional Immunology. You can find the link to that presentation here: https://youtu.be/UdcPNhrZk_o.
The conversation at The Exchange kicked off discussing that you can’t ignore the immune system and its integral involvement in day-to-day physiology.
The dialogue continues to come back with the focus on micronutrients & trace minerals, including selenium, choline and vitamin E. Both Dr. Bradford and Dr. Swartz discuss how they play into their research and the day-to-day work on the dairy farm. 6:57
Dr. Swartz has focused his research on mastitis, and he discusses the transition period and how one disease can lead to another in a domino effect. He talks about what role trace minerals play in cow health during this period. 10:01
We circled back around to Dr. Bradford, discussing that hundreds of receptors are expressed by cells appearing to be designed by nature to respond to nutrients. He shares that it dramatically changes the ways we can think about using nutrients. 14:25
As the discussion continues, both Dr. Swartz and Dr. Bradford dive into how the decisions made related to each other and what that means for your nutrition and health planning. 29:06
If you have questions about nutritional immunology or suggestions for future sessions, feel free to email anh.marketing@balchem.com.
Scott Sorrell (00:12):
Good evening and welcome to the Real Science Exchange. The podcast where leading scientists and industry professionals meet over a few drinks to discuss the latest ideas and trends in animal nutrition. Hello, I'm Scott Sorrell your host for tonight's conversation. One of our guests joining me at the exchange tonight is Dr. Barry Bradford from Michigan State University. Barry, you gave a webinar for the Real Science lecture series back in July, titled Feeding the Immunity Defenders, the evolving field of nutritional immunity. And one of the things you said really has prompted this discussion tonight. You said that your original focus was to make healthy animals more efficient, but that over the years you've learned that you can't ignore the immune system and its integral involvement in day-to-day physiology. Can you expand on that concept and give us a little preview of what we'll be talking about tonight?
Dr. Barry Bradford (01:04):
Thanks, Scott. Yeah. What really interests me is the integration of different disciplines. And I think this is one area where we're seeing traditional veterinary science and animal science converge, I think is really exciting.
Scott Sorrell (01:15):
Now, before we get too far into the conversation Barry, tell us a little bit about yourself and what's in your glass tonight.
Dr. Barry Bradford (01:22):
Well, Scott, I am enjoying an old fashioned tonight made with a Traverse city cherry bourbon, which I highly recommend. I am a recent addition to the faculty at Michigan State University. So I joined here in January of 2020, which had nothing to do with the onset of COVID. I just want to lay that out there. But I came here after being at Kansas State University on faculty for 13 and a half years. In this position, I'm in a 50-50 research extension role, which the extension piece is new for me. And I'm enjoying an opportunity to interact with producers more. Especially, well once it's easier to travel post COVID, hopefully.
Scott Sorrell (02:01):
Yeah, absolutely. So I see you've brought a guest with you tonight. Would you mind telling us a bit about him and, and how'd you come to invite him here tonight?
Dr. Barry Bradford (02:10):
Yeah, I'm really happy to have Dr. Turner Swartz on the meeting tonight as well. Turner has been working with me for the past couple of years as a post-doc after doing some outstanding training at Virginia tech, more in the mastitis space. And so he has been teaching me a lot about the immune system, about mastitis specifically, and we've really enjoyed the collaboration with sort of different areas of expertise.
Scott Sorrell (02:38):
Outstanding. Looking forward to getting to know Turner a little bit better tonight. My co-host here once again is Dr. Clay Zimmerman. Clay, can tell us what's in your glass tonight and perhaps, maybe elaborate on what impact that may have on your immune system.
Dr. Clay Zimmerman (02:55):
I'm enjoying some hard cider tonight. Scott Sorrell (03:00):
Once again. You're in a rut.
Dr. Clay Zimmerman (03:02):
Dude, I'm sorry. In honor of New York state though, our headquarters. So yes, I'll let Barry comment on the impact that may have on my end.
Scott Sorrell (03:13):
Sounds good. Hey, there wanted to let you know Clay I'm enjoying a, a Buffalo trace. This is, this is probably at least for now my, my favorite bourbon and I, I can't get that here where I live in Pennsylvania. So, a friend of mine Kim Jones, Kim is she was kind enough to get me some, some Buffalo Trace and she's kind of the wizard behind the curtain here behind Real Science Exchange. So I, tonight I just wanted to lift my glass to her and and thank her for, for the Buffalo trace.
Kim Jones (03:53):
So, well, thank you, Scott. I liked staying behind the curtain. That’s my favorite spot to be, back behind the curtain. does that make you the big head in front of the curtain?
Dr. Clay Zimmerman (04:00):
That's right. Yeah. So Barry, maybe, maybe to start us off, you were talking about, you know, your new position there at Michigan State a year ago and, and the, your role in extension. I'm curious, you know relating back to, to your presentation and, and all the work in nutritional immunology and that, that intersection. How, how, how are you integrating that into your extension role?
Dr. Barry Bradford (04:28):
That's a good question. I think, you know, a piece of what we work on, you know, some of it's kind of looking further down the road, so I wouldn't necessarily say that everything we're working on is something you can immediately take to the farm, but I think the area of inflammation in transition dairy cows is one that's sort of reaching a point of maturity where we can start to maybe apply some of the concepts on farms. And I know I've had a lot of discussions with veterinarians around the world about how can we start implementing some screening for some of the acute phase proteins that we use to assess levels of inflammation and transition cows. And then in turn, once we have that information, the harder question is what do we do with that information? And so that's kind of where we're at. And that's something that I'm hoping to gear up some in the state of Michigan here in this role.
Dr. Clay Zimmerman (05:20):
So do you interact a lot with, with the veterinary school there at Michigan state?
Dr. Barry Bradford (05:26):
Yeah, so that was an appealing thing to me about Michigan state is that there's an outstanding group of researchers in the vet school who work... on one of their core themes is inflammation and how that relates to metabolism. So Lorraine Sordello and Andres Contrares and Ángel Abuelo are all doing very complimentary work and interact with them a fair bit.
Dr. Clay Zimmerman (05:49):
So I was curious Barry, how the activation of the immune system, how does that affect nutrient requirements?
Dr. Barry Bradford (05:55):
Yeah, I think it's a good question. And one that we don't have a complete answer to, but we certainly know from work at Iowa State and other places that for example, glucose requirements or the use of glucose rises dramatically when there's a severe immune system activation. We know from complimentary work in other species, especially poultry, that amino acid needs for, especially the acute phase protein production certainly increase during that immune activation. And then just on a more global level, energy requirements increase by... in a lactating cow, if we put it on that scale, perhaps 10% to account for fever and the immune response, per se. So there's, there's clearly big impacts and, and perhaps the biggest impact is the drop in feed intake. So yeah, requirements change, but the intake and the nutrients coming in change more dramatically, even in many cases. So big, big change, that's going to affect the cow for sure, in terms of productivity.
Dr. Clay Zimmerman (06:58):
So from an amino acid standpoint, are there, are there, amino acids that are impacted more than others? By the immune system?
Dr. Barry Bradford (07:07):
Most likely, although we don’t have great data on that, I would say. Particularly in cattle, there is almost no data on that. We do have data on blood concentration, which is not the same as the requirement, obviously. But, there is some beef cattle work that shows that about seven or eight of the key essential amino acids drop in concentration by about as much as thirty percent in the first few hours after an endotoxin challenge. So that’s again, that's kind of an extreme model of a gram negative type of infection. But it at least gives us some indication that there some big changes there.
Scott Sorrell (07:45):
So Barry, kind of a follow up question to that. The people that are making sure that they they're feeding some extra nutrients, like vitamin E, selenium. There's even companies out there selling products that, that up-regulate the immune system. It, can you talk a little bit about what the cost, if any, of doing that is, or does the immune system just lay there? It's healthy and it's waiting for the pathogen? Or, or is there always a cost to, to having that immune system ready?
Dr. Barry Bradford (08:24):
Hmm, that's a terrific question. So I, I think a lot of times in marketing campaigns, it's kind of pitched that, you know, we can make the immune system strong and not over amplify it and everything's going to be perfect. And it doesn't really sound like biology to me, to be honest. We certainly know that maintenance of any type of cell, you know, growing B cells and T cells and stuff is going to take some nutrients. Now as a percentage of the total body mass, you know, those cells are a fraction, so it's not necessarily a huge, meaningful fraction. But I think it's a fair question of, can you, can you make the armed forces if you will, of the body, of the immune system more robust or ready to, to pick a fight, so to speak without that causing some kind of drag on the system. Either in terms of causing some negative effects associated with inflammation, or just turning up the sort of basal requirements of the animal because of that greater immune support. Theoretically, I think it makes sense that there has to be some trade off there. Now, could the trade off be such that if you prevent a 1% disease incidence, if you drop it from 8% clinical disease to 7%, you've easily paid for that perhaps. I mean, we don't even really have a good estimate of that, but I think those are questions worth thinking through.
Dr. Clay Zimmerman (09:53):
So Turner, you've done a lot of work in the mastitis area. How, how does nutrition interact with resistance to mastitis?
Dr. Turner Swartz (10:01):
So there's been quite a few studies done dating probably back in the eighties when they did association work that found that metabolism was associated with a whole bunch of infectious diseases, not just mastitis, but also metritis in early lactation dairy cows. So in my mind I like to view the, the transition period kind of like having a domino effect where you have one disease leading to another disease, leading to another disease leading to other cattle being culled. And so those are the problem cows, there's the cows with all the dominoes falling before, you know it, she's on the trailer. So really it, if the way I look at it for the most part is if we can improve metabolism in early lactation we can reduce the incidence of infectious disease. So I, I don't know if you want a more specific answer, but when you're looking at things like NEFA or beta hydroxybutyrate, the two main indicators for metabolic disease in transition cows. Those concentrations of those two metabolic parameters are associated with infectious disease. So as they go up, the risk for disease also goes up.
Dr. Clay Zimmerman (11:21):
There’s been a lot of work done with vitamin D and selenium, like you said, but are there other nutrients that you've been looking at related to this?
Dr. Turner Swartz (11:30):
There's been work done with trace minerals dating back into the 1980s. The vitamin E and selenium was done in the 1980s by Joe Hogan. Ron Erskin did some trace mineral work then. Both of those are antioxidants, and they’ve been found to improve immune function and increase bacterial defense, or bacterial killing abilities, of the immune cells during that time. Some of the more recent work that I've been focusing on, and some work that Dr. Brookmeir has done recently was a BHB infusion study where we actually infused ketone bodies into the cows intravenously, and we mimic ketosis. And we found that the beta hydroxybutyrate impairs immune function that way as well. And that's also been done using in vitro work as well, where if you culture neutrophils, which is a pretty, a pretty important immune cell, at least in context of mastitis. If you culture them with beta hydroxybutyrate, you can really reduce immune function, bacterial killing abilities.
Dr. Clay Zimmerman (12:41):
Barry, you you wrote a really nice paper that was, appeared in the Journal of Dairy Science back in 2016 Managing Complexity: Dealing with systemic crosstalk and bovine physiology. And you, you talked about nutrition 2.0 in that paper. Can you elaborate some on that and kind of where, where that whole area is right now?
Dr. Barry Bradford (13:14):
The, the whole concept behind that nutrition 2.0 idea was that in the first 100 hundred or 150 years of the field of nutrition science, the idea really was to discover what are all the essential nutrients that animals or people need. And then as we discover those, kind of work through how much do we need to consume, how much is the cow to consume, to prevent obvious diseases. And then, you know, in production animals that you know, evolved pretty quickly into, okay, now that we can prevent things like rickets... now what do we do to support greater productivity, greater growth, greater milk production, that sort of thing. And that's really been the driving paradigm and it's served great purposes, obviously. It's worked very well, but if you really look at how that whole system has worked, we're looking at nutrients as doing one of three things: either serving as a fuel that we can burn for energy; serving as some kind of building block, like calcium for bone, amino acids for muscle milk protein; and then co-factors for enzymes. So most, you know, trace minerals, vitamins go in that bucket. And again, it's worked very well. Those are all necessary things, but what that misses are some sort of second order effects of nutrients. So we clearly know in ruminants, for example, that what we feed animals is going to affect the microbiome in the rumen. It's true in humans as well on the hind gut. But that really wasn’t factored into that first round of thinking about nutrition. Yeah. You know, maybe we knew it, but it's not really accounted for when we consider what's the value of nutrient X. And that's just one example. So there are many other things now that we know that nutrients do. So they, they affect microbes. They can actually act sort of like a hormone themselves. So we now recognize that there are hundreds of receptors that are expressed by cells that appear to be designed by nature simply to respond to nutrients.
So that means a nutrient that doesn't even enter a cell can change the way that cell functions, which is I think pretty cool. But it, it, and it greatly changes the ways we can think about using nutrients. So it kind of takes away the idea of saying, well, we certainly have enough of nutrient X to allow for X amount of growth, and feeding anymore couldn't possibly help. Well, that's not necessarily true anymore because based on those router-based interactions, if you can increase the concentration of this in the bloodstream, you could still in theory, trigger physiological responses, even though that nutrient may not actually be used as a building block efficiently at that point. And that sort of thing also opens up all kinds of interactions that might come into play.
Dr. Clay Zimmerman (16:10):
So one thing you discussed in that, that paper was, you know, potential impacts of feeding the dam and perhaps affecting offspring performance. Can you elaborate on that?
Dr. Barry Bradford (16:24):
Yeah, that's true too. That's, that's another aspect of a second level, if you will. A way that nutrients can be used. So we now know that it's, it's simplistic to think of transmission or inheritance of traits and the way that sort of Watson and Crick defined it, where we have DNA that codes for certain proteins that are translated through messenger RNA and become a protein, right? So, that's certainly an important mechanism, but what that misses is the fact that there are many other regulatory steps in that process. And one of those is known as epigenetics. So, for example, we know from experimental studies in model animals, that exposure to cigarette smoke will change the chemical modifications on DNA and lead to inherited changes in what happens in the offspring, despite the fact that DNA itself, that the sequence of DNA isn't actually changed. And take that down to the level of nutrients now. Well, the chemical modifications that are important on DNA are of course modifications. They're they're chemical entities that come from nutrients, almost everything else, right? So methyl groups are coming from methyl donors. That's what did the key modifications of DNA. And we also have nutrients that could influence how the proteins that DNA is wound around are modified. And so, we have for example, ketone bodies can influence acetylation of these proteins and influence how available DNA is to drive gene expression. Okay, so this is all component of epigenetics. And so, choline is an example of a methyl donor, right? It can contribute methyl groups, can allow DNA to be methylated as the cells would like to methylate them. So, if the cell is deficient in methyl groups that can't proceed at a normal rate, and we know that methyl deficiencies can lead to these changes in epigenetics that influence the offspring. So, it's one of the frameworks that we're building some of our questions around in nutrition 2.0 is some of these multi-generational potential impacts of nutrition. Now, how many things can you point to where this has been absolutely clearly shown to work that way, that gets a little tricky. But we know the mechanisms exist, and we're trying to understand the real ramifications of that. By the way it Turner, I don't think this is really fair. You never had to say what you're drinking. You gotta fess up!
Dr. Turner Swartz (19:16):
I'm drinking tea, Barry. You know why? Because it has antioxidants in it, and that's what we're going to be talking about.
Dr. Barry Bradford (19:30):
Fair enough. Yeah.
Scott Sorrell (19:32):
Well, that's kind of a nice segue. Clay, if you don't mind kind of, I was going to kind of throw a question to Turner there, you know. When we're talking about nutritional interventions for supporting the immune system, what exactly are we talking about? What aspect of the immune system- is that both the innate, the adaptive? And then could you get a little bit more granular in terms of exactly what are we influencing? Like things like chemotaxis, and ross generation, phagocytosis those kinds of things.
Dr. Turner Swartz (20:01):
Yeah. So I think the answer to that is all of the above. So I think we're influencing both the innate and the adaptive immune system when you affect them nutritionally. In fact, there's a lot of work done with, with choline, for instance, that shows that if you increase choline supplementation, you increase T-cell proliferation. So one of my hypothesis would be, if you can do that, then you would improve the adaptive immune response. So for instance, a vaccine might be more effective in the cow that's supplemented with choline because their T-cells proliferate better. So I, I think you're influencing innate immune system and adaptive immunity. You have antioxidant defenses that are increased that helps prevent host cell damage from immune responses. So, when immune cells produce reactive oxygen species, those are great to kill bacteria, but they're also great to damage the host cells and the immune cells. So if you have way too much reactive oxygen species being produced, you end up damaging all the host cells. You end up killing some immune cells, which ends up impairing the immune response. So you kind of got to control that and by having some increasing antioxidant defenses, you can still have that robust immune response without having all of the collateral damage associated with it.
Scott Sorrell (21:31):
Okay. And then, so kind of building on that: what antioxidants are, are typically used or should be used in, in dairy rations?
Dr. Turner Swartz (21:41):
So choline would be an antioxidant that we talked about, but also your, your selenium, vitamin E. Those also have trace minerals, have antioxidant properties. Those are the ones that I'm aware of. I'm sure there are others. Maybe Barry can...?
Scott Sorrell (21:56):
You’d mentioned some of the research that's been done with trace minerals vitamin E it seemed relatively old to me. And I'm just kind of curious if, if that needs to be updated, and if so what's being done and are you doing it? You know, some, some questions along those lines
Dr. Clay Zimmerman (22:00):
I'm sure we all see, or Scott, you and I seem relatively old to Turner.
Scott Sorrell (22:09):
Yeah. Without a doubt. And that's a fact!
Dr. Turner Swartz (22:23):
Those studies were done before I was born. So they probably, to the best of my knowledge, I don't know of anybody that has updated them since. And there's been a lot of work done recently using like changing the source of selenium. I believe it's selenium, right? Where we’re using more of an organic source if I remember correctly. I'm not sure that the mastitis component of that has been updated?
Scott Sorrell (22:54):
Hmm. It seems to me like it might be worth kind of revisiting, right. Not, not only that was done a while ago. We've learned a lot since then. And we've got a far better diagnostics, you know? Yeah. We can do micro array and see what, what genes are being upregulated, downregulated with, with an, a microwave analysis. Just so many things that we can do. It just seems like somebody ought to be doing that.
Dr. Turner Swartz (23:20):
I think, I think Balkin should do something with their niacin product with, with the, using it for immune defense, with the mammary plan. I think you're probably missing something there.
Scott Sorrell (23:34):
Tell me a little more about that. What's the mode of action. What are you thinking?
Dr. Turner Swartz (23:40):
It has anti-inflammatory effects through it's through well, it's probably multiple ways, but through G protein coupled receptor. It's actually the same receptor that ligates BHB, but I think it has different effects. But it has anti-inflammatory effects. There was some work done that I don't really like the way they did the study. So I won't say, say how they did it. But there is some work that shows that it can reduce somatic cell count and help, help promote resolution.
Dr. Clay Zimmerman (24:12):
Hmm. So, so Turner, when are cows most susceptible to, to getting mastitis?
Dr. Turner Swartz (24:20):
Early lactation. So really there's two time periods. So after, right after dry off, and then again, right at calving. Those are the two most risky time periods for mastitis. The main reason for that is related to immune function or at dry off, we stop milking the cow- her udder gets really full. She starts leaking milk, you know, that teat is open, it's exposed. So it's pretty easy for bacteria to get up in there and establish infection. So that's really, that's why dry cow therapy and internal teat sealants got developed in the dairy industry was to reduce mastitis then. So now we've kind of shifted gears and now we're trying to get rid of mastitis in early lactation cows. And I, I suspect that most of it is related to immune function during that time period. And some of that is related to metabolism.
Dr. Clay Zimmerman (25:16):
So so what are your thoughts on dry cow therapy, as you were saying, or moving maybe to selective dry cow therapy? And how, how would, how should that influence our nutritional decisions?
Dr. Turner Swartz (25:34):
Well, that's a good question. Nutritional decisions to promote dry off might work. I've been a little bit hesitant to..cause some people like to feed high straw diets right at dry off to try to get the milk production down so that it dry, easier. I don't know how I feel about that. Cause sometimes you short them in energy, and I think I don't like doing that too much to stress the cow right at seven months pregnant. But my, my general opinion is we will be heading more towards selective antibiotic use. We will be heading away from blanket, dry cow therapy. Blanket dry cow therapy was never truly intended to be used as widely as it is. It was supposed to be a bandaid, a bandaid that just has never really been removed for, for decades now. So, I do think we'll move towards selective dry cow therapy, but you're going to have to change the way you manage your farm to make that work. So things like on-farm culturing, milk culturing, to see which cows are, which quarters are actually infected. Treat those ones and then leave the rest of them go. So you're going to have to change your management style to make that work in my opinion.
Dr. Clay Zimmerman (26:53):
Okay. Thanks. Barry, I heard a rumor that as a graduate student at Michigan State, you were on fire. Is there any truth to that?
Dr. Barry Bradford (27:04):
Yeah. I had to walk through fire and ice to get my degree actually. Yeah, we, we, I think one project I did, we did a glucose tolerance tests IV in 32 cows. And I think we broke it up into putting catheters in 16 cows a day. And of course, one of those days it ended up being like 10 below zero or something. And we were in a barn, but not insulated and it was insanely cold and you're wearing surgical gloves and like using ethanol and just freezing. So we had a butane heater in there, and of course you get colder through the day and you just kind of creep a little closer to it. And finally, one of my lab mates Steve Mooney, who's a very understated guy, just like Barry, you're on fire. And I said, w- what? You're on fire. And I'm like, no, he's like, you're, you're really on fire. So I looked down and sure enough, the back of my leg is on. And then another time I was helping somebody in the summer at the beef unit and there's a huge walk-in freezer and I'd put some samples away for him and went to leave. And the the little latch that lets you out with broken. And so I was stuck in the freezer. Thankfully, somebody found me in about five minutes. I started beating on the door and somebody was there, but that that would not be a fun way to go.
Dr. Clay Zimmerman (28:20):
You survived both extremes there!
Scott Sorrell (28:28)
We were talking with Kevin Harvard, Kevin Harvatine last time and he was sharing that with us. That was, that was quite a funny story. He told it very much the way you the same way you did as well, that was awesome.
Dr. Clay Zimmermand (28:37):
So another thing you discussed in the managing complexity paper, you talked about maternal transfer through colostrum. Can you elaborate on on some of the work that's been done there and what's being transferred through colostrum?
Dr. Barry Bradford (29:06):
Yeah, sure. I'm I may hand the baton to Turner a little ways through this cause I'm not, I don't consider myself a huge expert on this, but you know, one thing that sets cows apart from some other species's is the degree to which the calf relies on milk or colostrum transfer of antibodies to the offspring, as opposed to in-utero transfer. At least that's my understanding. And I think it's interesting question from a management standpoint, as well as nutritional you know, what can we do to help the cow have adequate colostrum yield. But also nutritionally, can we do things that support antibody production, antibody transfer into that colostrum to get the calf what they need. And then, you know, if that's an efficient process, can we design, you know, vaccination protocols that actually take advantage of that transfer process and actually provide the calf with immunity through the cow and how we design delivery of vaccines. Turner rescue me here.
Dr. Turner Swartz (30:12):
I think you got it right. The only thing specifically, if you, if you're interested. The colostrum antibodies, they activate receptors on the B cells, which pushes them into anergy. So then they stopped producing antibodies. So that's why... we don't know that yet in calves, but we know that in humans. So that's why colostral antibodies interfere with vaccine responses and early newborn animals.
Dr. Barry Bradford (30:41):
Did you say anergy or is it just pronounced energy real weird cause you're not a nutritionist?
Dr. Turner Swartz (30:46):
Yeah. No, “anergy”. They make them, they shut them down.
Dr. Barry Bradford (30:50):
Okay. Can you just say “shut that down” instead of trying to make us feel dumb? That's okay.
Dr. Clay Zimmerman (30:48):
Barry, you want to elaborate some on maybe, maybe some research you're doing in your lab or some, maybe some future plans?
Dr. Barry Bradford (30:58):
You bet. Yeah. I'll share a couple of arms of things we're doing so on this whole nutrition 2.0 thing. One thing we're working on is what you might call trying to Westernize Eastern medicine. So I, I think if you, if you just go and look in the literature on Google scholar or something and just type in, phytogenic nutrients or something like that, you'd just be blown away by the number of studies going on right now with different Chinese plants, different superfoods, if you will. And trying to understand in mice models typically what these either components of foods or whole foods that are supposed to be health- promoting actually do with animals.
31:56):
And I think that's good. And I think it's kind of one of those areas where between sort of quack, online sales people, and people coming out with products in the animal sector too early, people can get a bad taste in their mouth that it's snake oil and a it's all a bunch of just marketing drivel. And there's nothing to it. And I think there has been a lot of stuff out there, especially on the human side that has not been well-proven. But that doesn't mean that there's not some real interesting biology there that can be better understood and actually put to use. And so we're interested in can we come up with some screening models to help us dial in on what are some of these phytogenic compounds that really do hold promise for impacting animal productivity and health? And I think probably the most likely application I could envision is having a, a low cost, maybe, maybe economic, but I really mean cost to the animal as much as anything sort of low level support for the immune system if you will.
(33:04):
Maybe it's through a mild stimulation that lets the animal respond more robustly to a challenge or helps them make it through a disease challenge in better shape or with less dramatic challenge to health or less dramatic hit to productivity. So I think there's real promise. There is it just, there's tens of thousands of compounds, probably hundreds of thousands of compounds. And what makes it even more complicated is typically these plants are not making one compound in great quantities. They're making 10 compounds that collectively have some interesting effects. But pulling out one at a time may not show that effect. So it makes it really hard to do the type of science we're used to doing, but I think there's a lot of promise there. So I think it's worth trying to tackle those kinds of questions. But you know, one of the problems is you can't test 10,000 things realistically in livestock. So we need to kind of figure out what's worth taking to the whole animal. And that's one of the things we're working on. Turner, why don’t you talk through the other big thing we're tackling right now.
Dr. Turner Swartz (34:09):
I know we're, we're doing a study with choline right now that's looking at the antioxidant and anti-inflammatory effects during a intra-mammary challenge in early lactation dairy cows. Our, our hypothesis is essentially that these cows will have less inflammation in the mammary gland during a lipopolysaccharide challenge, which lipopolysaccharide is just a component of e-coli. So we're mimicking an e-coli- mimicking a, an e-coli infection in these cows. And we're taking a bunch of tissue samples and looking at both mammary responses as well as liver responses, because that challenge actually impacts them systemically as well as locally in the udder. The other thing we're looking at is we're doing a calf study. So we're, we're supplementing these transition cows with choline during the pre-partum period. And then we're going to see if these calves are ended up being healthier, does their immune system function better? And we're going to put a mucosal vaccine into them. So, an intra-nasal vaccine, we're going to measure responses to that vaccine to see if they respond better, have more more immunity towards respiratory pathogens.
Scott Sorrell (35:24):
So turner, you mentioned that you're mimicking e-coli. Would you anticipate a different response to other pathogens other than e-coli? And what might that be?
Dr. Turner Swartz (35:38):
Yeah, so mastitis is a great way to model infectious disease, but you're modeling so many different types of diseases in mastitis. Everything has a different response. So we have to kind of keep that in mind. To me that's an area in the mastitis field, as well as the nutritional field that is really underexplored. So we really don't know if maybe a supplement helps with this type of infection, but doesn't help with another type of infection. So we have gram negative pathogens, which are like your e-coli, Klebsiella, those type of coliform mastitis...they tend to cause a really acute inflammatory response. So a lot of times when you talk to a farmer about coliform mastitis, it's that really chronic cow or not chronic, excuse me, really toxic cow. She's really sick, got a high fever. She's off feed. That's your kind of your classic gram-negative mastitis.
(36:38):
With that said now there are a lot of cows that get E-ecoli mastitis and you never know it. So the majority of mastitis is cleared. It's called, we call it spontaneous cure where the immune system just kind of comes in and takes, takes care of it, kills the e-coli and the cow gets over it. So we're trying to increase those cases, you know, where, where we actually improve the immune system to clear these infections. The other type of mastitis would be gram positive infection. So your streps and your staphs. They tend to cause a lot lower level of inflammation. They're not going to be your toxic cows. They're going to be kind of chronically infected cows a lot of times. But the level of inflammation isn't nearly as obvious. They're probably still consuming feed pretty well. Maybe not as, but not but maybe just have inflammation in the quarter. So they're very different immune responses.
Scott Sorrell (37:35):
Now is your hypothesis that you're up-regulating both the adaptive and the innate immune system, or is it more one or the other, do you have an hypothesis on that?
Dr. Turner Swartz (37:46):
I, I think you're affecting both. So with the choline study, I think you're referring to, I think it will be effective. I think we'll be affecting both. If you improve adaptive immune responses, you're going to improve, should improve, innate immune responses as well. Cause the adaptive immune cells are, are helping to support the innate immune response. So if you improve T-cell responses and you increase certain cytokines that are beneficial to boost the innate immune responses, you will also see that effect as well. So they go hand in hand. The immune system is very complex in cell to cell interactions.
Scott Sorrell (38:24):
No, no completely understand kind of the seed of my, my, my question was that I, I, I, I believe I've learned somewhere along the line that there are some bacteria specific pathogens that are less susceptible to the innate immune system, specifically neutrophils in the mammary gland. Yeah.
Dr. Barry Bradford (38:43):
Clay has got a-… I'm curious, you know, you guys have kind of started to weight into research in immune responses to, you know, your kinds of products. One of the challenges when I talk with different companies working to advance R & D programs is how do you try to tackle this huge immune system? Like if you want to investigate, does our product influence immunity? Where do you start?
Dr. Clay Zimmerman (39:06):
It's a great question, Barry. Honestly, we work with people like you to figure it out, right? We want to work with the best minds that are out there to deal with that. So we're really, honestly just kind of getting started in this area. But no...
Dr. Barry Bradford (39:15):
Yeah, I don't think there's right answer. I just think it's a difficult problem. Even if you go to the extreme of doing expensive challenge studies where you actually having animals go through a true disease process... to Turner's point, you just made, you know, you may do a very intense, very difficult study and it's on one organism, right? So can you even extrapolate that to other organisms? Well, maybe if they're all gram negative or something maybe, but then we have viruses. We have gram-positives, we have all these other things. And I, you know, we, we've done, sorry we've done in vitro models and I'm, I don't throw those under the bus at all. I think we can use those, but I do think it's difficult to extrapolate some of that data to, Oh, this means an animal’s gonna survive a challenge better.
Dr. Turner Swartz (40:16):
And that's why I think we need some large epidemiological studies where the main outcome is just disease incidents. And maybe you can figure out what's actually causing the disease. So if you're looking at mastitis, maybe you sample the cows that have clinical mastitis to figure out what the pathogens were. Can we do that on a large scale in field trial? I think you could help answer that question better.
Dr. Clay Zimmerman (40:34):
Yeah, no, that's a good point. And we're starting to do some work in that area as well...with some larger field trials. That's a really good point.
Scott Sorrel (40:45):
I was just going to follow up on, on Clay’s answer- he's absolutely right. We do rely on people like yourself, Barry, and you know, and it all starts with relationships. Right? Many times i's not always an intentional question. It's a conversation like we're having today, right? After a science conference, over a few drinks, it's a that's that's happened a lot. And so I just found it interesting. Right. And it gives me an opportunity to put plug in for the real science exchange. So yeah,
Dr. Clay Zimmerman (41:18):
I agree. Yeah. Okay. So Barry, I'm curious, we hit on this a little bit earlier about you know, nutrition 2.0 and the intersection of, you know, nutrition and immunology and the uh... so it should be a Dairy NRC [Nutrient Requirement of Dairy Cattle] publication coming out this year. What advice would you have for either this committee or committees moving forward as far as as looking at the impacts of of immunology related to, to the NRC?
Dr. Barry Bradford (41:56):
Yeah. I know one of the benefits of teaching- I taught an undergraduate fundamentals and nutrition class for 13 odd years. And one of the benefits of that is it helps you keep fresh in your mind how this simple thing that we call a “requirement” is actually not really that simple once the job is handed to you to set it, right? So in theory, it sounds great to say, okay, well, let's just do a few studies and figure out at what point an animal stops benefiting from more of this nutrient. So conceptually, that sounds good. Okay. So what are you going to measure to see if the animals are benefiting more? Ok so with livestock the easy thing to measure, well, in humans for that matter (and growing humans), would be growth rate and milk yield in a lactating animal. And beyond that, it starts to get prettydarn tough. Actually, you could say, well, okay. If the lack of a nutrient makes an animal completely infertile, we can pick that up. Absolutely. Okay. But if you're talking about that last 10%, that's further improving fertility. But they don't go from being completely infertile to fertile. That's pretty hard to pick up too. And if you know anybody who's done any kind of research in fertility or go read some papers and journals or dairy science with AI protocols, they're using hundreds of thousands of animals for treatment, right. Because it's very hard to show a real difference. So now think about feeding graded levels of nutrients with hundreds of thousands of animals per treatment. It's just not practical, right? We have the same problem on the health side. If you start saying: at what level of nutrient do you see no further benefit and health? Well, how are you going to define that? So, to Turner's point a minute ago, in a perfect world, you know, maybe you could have 300 farms. And you could feed graded levels of a nutrient X and everything else is the same. Well, that's completely impractical. You know, in that scenario, you could maybe actually look at disease incidence, but we can't really do that. So what can we do? Well, the reality is continuing through the upcoming NRC. I'm sure those requirements are going to be based primarily on growth and productivity data, right?
(44:27):
Because that's what we have access to, and we can actually do studies to see graded changes in. However, you know, people who have written these over the years will acknowledge, if you read it carefully. And don't just look at the numbers that look, there may be pieces of evidence here from individual studies, where they fed more vitamin D for example, we see some hints of better transition health. And so that, that would be an example of a nutrient where I think some health studies have had some influence, but there we're talking about, you can change it by threefold, and you know, it's going to change your diet costs by 1% or something. We can't feasibly do that with every amino acid, for example, every essential amino acids. So it just becomes really difficult. It's easy to throw stones, right. But they need solid evidence to build these stories on.
(45:20):
But it does, it does come back to the point of if you are a nutritionist and it's your entire job to feed these animals the best you can, you should absolutely rely on that excellent expert advice that's in the NRC, but then you also need to apply your own wisdom and experience and knowledge to your given situation. And if you're working with a herd that has a high disease incidence, and there's maybe a study here or there that suggests feeding nutrient X at a slightly higher level might help with immunity. Maybe that's something worth exploring instead of just saying, well, Nope, here's the requirement. We know that to a T, story closed.
Dr. Clay Zimmerman (45:48):
Turner, do you have any thoughts on that?
Dr. Turner Swartz: (45:50)
No....I was going to say that's why you need to study immunology and not nutrition.
Dr. Barry Bradford (46:06):
Turner's good at memes... We should have had this one ready, but he got sucked into a study on some alfalfa a year and a half ago. And I'm trying to get some work one day and I get this text from Turner and it has a picture of him and alfalfa field, just looking at a flake of alfalfa, just studying it. And he said I'm officially a nutritionist now, check that box now. So you have no reason not to comment, Turner. You’re in that club.
Scott Sorrell (46:54):
So guys, I, I just heard them call last call. So it's kind of time to wrap this up. It's been fun kind of last comments here. What are two things that you'd leave our listeners with as a take home message and, and, and while you’re talking through that, talk about the metabolic cost of disease and what should producers do on the farm to reduce that. And I'll leave it up to you guys who wants to answer what.
Dr. Barry Bradford (47:23):
I have one, one thought first and then I’ll turn to Turner. One, one point that I has, I think been a consistent theme of, of our research program is I think you do need to scrutinize feed additives very carefully through most of lactation- well throughout the diet. I mean, it's, it's a, it's a commodity business. It's hard to make a living at it, for sure. You shouldn't be throwing money away. Okay. That being said, the same logic that we apply to a mid-lactation diet, we shouldn't necessarily apply to transition cow diets, right? So there are things that we absolutely can afford to do for six weeks through the transition period that if you look at them on a cost per year, instead of a cents per cow, per day basis, compared to the cost of one more sick cow out of a hundred is a good investment, right. And you still need to evaluate: is it just, is it just pure marketing behind this product or is it a real science. But if there is some evidence that this can improve metabolism, immunity, appetite of those cows, it's likely to pay off just because of the many, many ripple-over benefits on reproduction on productivity in cows that transition well. So that's one big take home in my point of view.
Dr. Turner Swartz (48:41):
Yeah. So I would agree with that. I think anytime you can improve immune- or improve metabolic function during that transition period, it's gonna pay off in the long run in terms of reducing mastitis incidents, reducing other diseases. So I, I'm a big believer in that anything we can do to cows pre partum to help set them up better postpartum is a huge, huge benefit. The other thing I would add to it is that, for at least for mastitis, not one size fits all. So mastitis has a bunch of different pathogens in it, and what's a problem with one farm may not be a problem on another farm. And so we have to design solutions for each specific farm. So I think when we're thinking about things nutritionally or even pharmacologically, whatever it is, that solution needs to be tailored for that farm, with the hopes of solving that problem without having any consequences. Increasing the incidence on another type of disease, for instance. So one size doesn't fit all. That's my takeaway.
Scott Sorrell (50:00):
No, that's a, that's a great comment Turner and, and a great one to end on. And so I, I want to thank both of you. You've been both great guests. I’ve have enjoyed spending some time with you look forward sometime, Turner, meeting you in person someday when we get all this behind us. And so thank you for joining us here tonight. And I'd like to thank all of our loyal listeners for stopping by to spend some time with us once again, here at the exchange. If you'd like what you've heard, please remember to drop us a five star rating on your out. Also, hit the subscribe button so you'll receive alerts for future podcasts. And if you’re so inclined, glowing reviews are always welcomed. Our scientific conversations continue on the real science lecture series of webinars. Please visit balchemanh.com/realscience to see the upcoming events and past topics. We hope to see you next time here at the Real Science Exchange, where it's always happy hour and you're always among friends.