Dr. Baumgard begins with an overview of the structure and function of the gastrointestinal tract. More than 75% of an animal’s immune system resides in the gut. The focus of this webinar is how heat stress initiates leaky gut, how that leaky gut then influences the immune and hormonal systems, and ultimately, how that reduces productivity. (0:22)
This Real Science Exchange podcast episode was recorded during a webinar from Balchem’s Real Science Lecture Series. You can find it at balchem.com/realscience.
Dr. Baumgard begins with an overview of the structure and function of the gastrointestinal tract. More than 75% of an animal’s immune system resides in the gut. The focus of this webinar is how heat stress initiates leaky gut, how that leaky gut then influences the immune and hormonal systems, and ultimately, how that reduces productivity. (0:22)
Dr. Baumgard compares the metabolism of a cow 200 days in milk to a cow 10 days in milk. The 200-day cow is experiencing ad libitum intake and gaining weight. Her insulin levels would be high, and NEFAs would be low. On the other hand, the 10-day cow is experiencing suboptimal intake, and her insulin levels are the lowest they’ll ever be during the production cycle. Body tissue is mobilized, and NEFAs will increase. Research shows it takes 72 grams of glucose to make one kilogram of milk. Any disruption to the gluconeogenic pathway has the potential to decrease milk yield. (6:38)
Heat stress is estimated to cost the US dairy industry $1.7 billion each year. Regardless of climate change, heat stress will continue to be an issue because all economically important phenotypes in animal agriculture are heat-producing processes. Dr. Baumgard’s lab has been investigating the biology of heat stress to implement more effective mitigation strategies. (9:09)
How much of the reduction in feed intake during heat stress explains the reduction in milk yield? A pair-feeding experiment comparing thermoneutral to heat-stressed cows showed that about 50% of the reduction in milk yield during a heat wave is due to a reduction in feed intake. The thermoneutral cows lost weight in response to decreased intake, and their NEFAs increased. Heat-stressed cows did not have an increase in NEFA. Heat-stressed animals fail to mobilize adipose tissue despite their endocrine profile predicting that they should. However, insulin is high when we would expect it to be low, and that response to heat stress is highly conserved in all species. (10:43)
Heat-stressed cows produced about 400 grams less lactose per day than their pair-fed thermoneutral controls. This is nearly a pound! Is the liver producing 400 fewer grams of glucose each day? Or is some other extramammary tissue using more glucose per day? Dr. Baumgard’s work suggests that the immune system is where the 400 grams of glucose go in heat-stressed animals. During heat stress, vasodilation at the body surface occurs, with concomitant vasoconstriction in the gut. The gut epithelium is very sensitive to reduced oxygen delivery that would result from the vasoconstriction, and tight junction proteins do not function properly, resulting in a leaky gut. This results in an infiltration of antigens into the body, which causes an immune response. (15:36)
Dr. Baumgard details how insulin fits into these immune responses via the Warburg effect. An activated immune cell prefers glucose and needs it in high quantities. The activated cell switches from the Kreb’s cycle to generate ATP to aerobic glycolysis. This requires high insulin. The immune system requires approximately one gram of glucose per kilogram of metabolic body weight per hour. (25:03)
By far, the biggest impact a dairy producer can make to alleviate heat stress is to modify the environment physically: shade, fans, soakers, misters, etc. Investing in cooling cows improves production efficiency and profitability, summer fertility, animal welfare and health, and sustainability. Other important heat abatement considerations include adequate water availability, reducing walking distance to the parlor and time in the holding pen, and improving ventilation. Dry cows should also be part of any heat abatement strategy, as the benefits of cooling dry cows extends far into lactation. Dr. Baumgard also discusses different dietary management strategies for heat stress situations. (32:43)
In summary, heat stress decreases almost every metric of productivity and costs everyone in the industry. Reduced feed intake is only part of the problem. Heat-induced leaky gut results in biological consequences incredibly similar to any other immune activation, such as mastitis or metritis. For dairy producers, heat stress abatement should by far be their biggest priority. Once those infrastructure improvements are in place, dietary interventions are another good strategy to minimize the negative consequences of heat stress. (47:43)
Dr. Baumgard takes questions from the webinar audience. (49:22)
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Balchem (00:00):
The following podcast is taken from a webinar presented by Dr. Lance Baumgard from Iowa State University, titled The Benefits of Mitigating Heat Stress in Dairy Cows. To view the full webinar and access the slides referenced during this podcast, visit balchem.com/realscience and use the search bar to jump to this webinar from May 12th, 2020.
Dr. Lance Baumgard (00:22):
So this may seem strange to start off a heat abatement talk about the gut, but we'll, I'll, I'll, I hope you'll follow along with me and we'll, we'll, we'll get to the gut here eventually. But the idea that an unhealthy intestine or unhealthy gut is the epicenter of, of an animal's overall health is not new, right? So you'll see in a second how we whittled our way down to the gut during heat stress. But, but like I said, if, if you've, if, if you ever experienced any type of gut problems and a huge percentage of, of adult population due, you'll understand why. If the gut's not healthy, the the animal's not healthy. Just a quick reminder of what the gut is. The GI tract, the gastrointestinal tract is a tube running from the mouth to the anus. And technically, everything, everything inside that tube remains outside of the body.
Dr. Lance Baumgard (01:11):
So that means the breakfast you just had a few hours ago, most of it was remaining outside of your body. It takes a couple hours, two or three hours before those nutrients are absorbed. It's not until the animal that those the food stuff is absorbed that actually becomes part of you. Right? So and we as nutritionists and veterinarians oftentimes think of the GI Shack. Primary job is to digest and absorb valuable nutrients. And clearly that's an important job. But if you're a strict immunologist, you'd probably argue that a more important job of the GI track is to keep unwanted molecules from entering or infiltrating into the body. Most of the things inside of a person's GI track or an animal's GI track, they don't want in right? Parasites, pathogens, enzymes, acid, et cetera. If these things infiltrate the barrier of the gut, they have an opportunity to stimulate the immune system. And here, here's just a, a, a, a cartoon of what the VII structures look like. Of course, these vii they're, they're intent is to markedly maximize the surface area of the gut. And there might be, oh, thousands of different cells that are lining this particular the lie, okay?
Dr. Lance Baumgard (02:26):
And because of this strategy, the animals use to maximize the surface area of its gut it, it, it, it, it really does increase the, the size of the, the surface area. And, and, and two other epithelial that all animals have are, are the skin. And I'm just using the skin as a reference, 'cause I think everyone has a good idea of how much surface, area of skin there is. This is a human example. Now, there's about two meters squared of surface area in a human, human skin. The lungs you know, because of the, of VII of the lungs, there's substantially more surface area of the lungs compared to the skin. Because of these modifications in the structure of the gut, the mucosal folds, the vii and the microvilli, the surface area of a human's GI tract is about 150 times that the size of the skin, right?
Dr. Lance Baumgard (03:16):
That's an enormous increase in surface area. Now, this is, again, a human example. So you can imagine then how much larger the surface area of, of the gut of a ruminants gut is, right? Because obviously the, the pre gastric fermentation compartments, this number might be 10,000 times the size of, of the skin surface of a cow. I, yeah, I don't know. But regardless, it's, it's an enormous VA number. And again, if you're looking at the a human's GI tract, if you laid down the GI tract and, and flatten its surface area out, it would be about the size of a doubles tennis court. So remember all those, there's the pathogens, antigens, et cetera, that are in gut. In fact, you have, you have more microbes in your gut than you do cells of your body. So, you know, the old joke about who's really the host and who's really the the parasite here is, is clear, right? And, and because of all these microbes, even even the non-pathogenic ones, if they infiltrate into the body, they're gonna stimulate an immune response. So it's not surprising in that a, a majority of the immune system evolved from the gut. Even in the most simplest creatures, the, their immune system mostly resides in their gut. And still today, over 75% of an, of an animal's immune system resides in the gut. It's because it's massive, right? And it's constantly exposed to potential pathogens.
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Dr. Lance Baumgard (05:55):
Now, my group today we're gonna be talking about how heat stress in initiates leaky gut and the consequences of that. We've since then extended the biology of, of leaky gut to looking at the transition period and feed restriction and high gut acidosis. And we're just now starting to look at mycotoxins, but we're not gonna talk about these other insults to the gut. We're also very interested in calcium metabolism, but we're gonna focus in today on, on how heat stress initiates leaky gut and how that leaky gut then influences the immune system metabolism and the hormonal system, and ultimately how it reduces productivity. A very quick review though of, of metabolism an animal that's an ad lib feed intake and gaining weight. What's, what's from, from a dairy perspective? Let's let's use the cow that's 200 days in milk as our example.
Dr. Lance Baumgard (06:52):
She's in a positive energy balance. She's adlib and fed insulin levels would be high, okay? That's, that's the hormone that's reflective to, to feed intake. And because of the hyperinsulinemia there's a decrease in unnecessary fight fatty acids. And so she's putting on condition insulin is very potent lipo hormone and very potent anti lipolytic hormone. So she's gaining weight, she's gaining condition, and the hormone that's primarily responsible for that is insulin. Now, let's compare her to the animal that's suboptimal feed intake. For example, the cow that's in the 10 days in milk, okay? She's only week after calving. She she has the lowest levels of insulin in her entire lifetime, will be during that short window of time. It's, it is this hyperinsulinemia that allows her to mobilize adipose tissue, not necessarily fine fatty acids go up. So she's losing body condition and she's losing body weight primarily because of the decrease in insulin, okay?
Dr. Lance Baumgard (07:52):
So that this is normal metabolism that I'm sure we all had to memorize back in, back in nutrition class. You know, and the reason I'm emphasizing this is 'cause you'll see how, how there, how different this is when, when we're talking about heat stress. Okay? So also just a very quick reminder of how important glucose is, especially to lactating ruminant. So glucose is the, is primarily made from propane. Of course, propane is one of the bottle fatty acids coming outta the liver. So this monosaccharide glucose is the precursor to lactose. So this is milk sugar. This is a disaccharide. And the reason why this is important is because the amount of lactose made determines, primarily determines the overall milk healed. In other words, lactose is the primary osmotic regulator of milk healed. So the more lactose an animal makes the more milk she'll she'll provide.
Dr. Lance Baumgard (08:50):
And we know that it takes about 72 grams of glucose to make one kilogram of milk. So if anything disrupts this pathway, either back here in the rumen or if anything reprioritizes the use of glucose other than the m gland, it has the opportunity to cause, cause milk production. Okay? So obviously we're all interested in heat stress for a variety of reasons. Animal welfare being being key. But the, the other reason, of course, is economics. And the dairy industry is very sensitive to heat stress. Most of all the animal agriculture industries at about $1.7 billion a year globally. I've read estimates that up to $500 billion a year, it's hard to wrap your head around. And even hard to calculate, obviously, it, it'll get worse in the future. So it's already a huge problem. I wanna, I wanna emphasize that it's already a massive economic problem.
Dr. Lance Baumgard (09:44):
It'll get worse in the future if climate change continues. Even if climate change is not going on. Even, even if climate change doesn't continue, heat stress will become more of an issue in the future because of how what our genetic selection continues to emphasize. All of the, all the phenotypes that are economically important to us in animal, animal agriculture, milk synthesis, lean tissue accretion, pigs per cell, et cetera. These are all heat producing processes. So the amount of heat and animal produces today of our farm animals today is substantially more than what it was 40 years ago. And, and the likelihood of our grandchildren's farm animals producing more heat than our current animals are, is, is, is, is almost certain. So in other words the, the temperature at which a high producing animal becomes stress or heat stress is going to continue to go down.
Dr. Lance Baumgard (10:43):
So we have to figure out what's going on in, in try to understand the biology of heat stress so we can implement mitigation strategies. So one of the first experiments that Rob and I did at Arizona looking at heat stress was how much of the reduction in in feed intake explains the reduction in milk yield. So in other words, all animals have a reduction in feed intake when they become heat stressed, right? And forever we've always assumed that the reduction in feed intake explains why there's a drag in productivity during the summer. So we implemented a, what's called a pair feeding experimental design. We, we heat stress cows we're, we record how much the, of a reduction in feed intake they have, and then we, we pair feed a group of thermal neutral cows. So in other words these cows are remaining at 18 degrees centigrade, 68 degrees Fahrenheit, and we only allow them to consume the same quantity of feed that the heat stress cows were consuming.
Dr. Lance Baumgard (11:47):
So they're paired, right? They're paired to the heat stress, okay? So in this particular experiment, there's about a 30% reduction in, in feed intake. And, and now all the, all the data I'm gonna show you for the rest of the 45 minutes here is not confounded by differences in feed intake. There, there, the, the direct result of, of heat stress. So here's, here's the para fed cows. Remember the blue line is thermo neutral cows consuming 30% less feed. There was a reduction in feed intake of about five kilos, right? Because they're eating less feed. But now, only after about the first 20 or four or 48 hours these cows will implement homeotic strategies to max to maximize milk yield, right? They're, they're put, they're here to make milk and they'll, they'll do everything in their power to do so. The heat stress cow, there's a, just a continuous and progressive decrease in milk yield for about six to seven days until it finally plateaus.
Dr. Lance Baumgard (12:49):
So here's what we understand from this simple experiment is that all the area between these two lines has everything to do with simply being heat heat stress, right? And, and by doing some, some math, we know about 50% of the reduction in milk yield during a heat wave is due to a reduction in feed intake. The other 50% though, at this stage of the presentation, we don't know what explains that what's causing this other 50%. And we've essentially spent the last 15 years of our lives chasing this down. So as the name implies, heat stress, right? Stress is associated with the, the, the stress response. You have an increase in CRF and ACTH and eventually an in increase in release of, of cortisol. And, and this is a, a dairy cow experiment where we saw about a almost a 60% increase in, in cortisol.
Dr. Lance Baumgard (13:43):
And of course, cortisol is a very catabolic hormone, right? It's responsible for breaking down different tissues. And not surprisingly then animals during the both animals, the para fed thermo neutral and the heat stress animals lose a considerable bottom body weight in that week or nine days of heat stress, right? Almost, almost a hundred pounds of body weight loss in a week. So this is a hypercatabolic condition. And as you'd anticipate when you, when animals are in thermal neutral conditions and consume 30% less feed and lose almost a hundred pounds of body weight, they're not necessarily five fatty acid concentrations go up. So that, here's the nefa on the Y axis, and of course, not necessarily fight fatty acids are a product of, of adipose tissue mobilization. The, the para fed cows will mobilize adipose tissue in an effort to spare glucose for the synthesis of milk.
Dr. Lance Baumgard (14:38):
So this is, this is normal. This is a hundred percent anticipated. The heat stress cows do not. And it turns out that there's a variety of models where heat stress animals just simply fail to mobilize adipose tissue despite the endocrine profile suggesting or predicting that they should increasing cortisol, epinephrine, glucagon, et cetera. So these animals should be breaking down adipose tissue, but they don't. And again, this is conservative amongst a variety of species, ruminants, pigs, chicken rodents, humans something is preventing adipose tissue mobilization during heat stress. Well, what's the most obvious exam or explanation? It's insulin, strangely enough, despite the fact that animals go into negative energy balance, they lose body weight. And there's this hypercatabolic endocrine profile. There's also the strange increase in insulin. I want to emphasize that again, this is weird because the animal's gone off feed, right? 30 40% reduction in feed intake.
Dr. Lance Baumgard (15:36):
What's explaining this increase in insulin in, in dairy cows, what turns out it happens in a, a variety of species. In fact, it's, I think it turns out it increases in, in every species ever evaluated beef pigs, rodents, rabbits, humans, how even snakes, when they become heat stress, there's an increase in circulating insulin, both basal and stimulated insulin response stimulated by a glucose tolerance test, the GTT. So this is a highly conserved response, and it's just really metabolically strange, okay? So the nice thing about dairy cows, of course, is that we can do an accounting of glucose every time we milk 'em. So we know that the perfed cows, or the, I'm sorry, the heat stress cows are secreting approximately 400 grams less lactose per day than the perfed controls. In other words there's almost a pound. Remember there's 454 grams of glucose in a pound, and the heat stress cow is cons is, is secreting about a pound less of carbohydrates less than the per fed neutral control.
Dr. Lance Baumgard (16:48):
So the question we had next was, okay, is the liver producing 400 grams less of glucose per day? Or is some other extra mammary tissue utilizing more glucose per day? So we, we utilized we collaborated with a friend, Matt Waldron, and looked at using stable isotopes, looking at hepatic a whole body glucose production. And I, I tend to get bogged down in the slides, so I'm, I'm not gonna do that. But the main thing here is that the para fed and the heat stress cows have a, a decrease in their capacity to make glucose compared to thermo neutral, neutral adlib conditions. But the important thing here is the decrease in glucose production is similar between the two, between the two environments. So what does that tell us? It tells us that it's not the liver's fault, the liver's making glucose, it's, it's responding to the inogenic hormones.
Dr. Lance Baumgard (17:42):
And, and importantly, the hyperinsulinemia is not shutting down the hepatic glucose production. So this, this, we, you know, we discovered this back 10, 12 years ago now, and for a long time we assumed that the muscle was a, was increasing its glucose consumption. And I'm gonna try to convince you now that probably the, probably the, the increase utilizer of glucose is, is the immune system. And, and to get an idea of why that there's an immune response during, during heat stress, you gotta understand how heat stress affects the gut. Okay? So every animal when they be, when they start to accumulate heat, including humans vasodilates at the skin, that's why when you go to the beach or you go to the gym or you bale hay or whatever, you, when you start to become hot, your face gets red, your skin gets red, you're doing that because you, you're trying to vasodilate and to maximize heat dissipation, okay?
Dr. Lance Baumgard (18:41):
But if you're gonna have vasodilation that's such a large tissue, like the skin, you have to vasso constrict somewhere else. If, if you didn't, you'd have, you'd die from low blood pressure, not gonna end up blood back to the, to the heart. And the area of the body that basal constricts during heat stress is the gut. So you have this massive vasodilation at the, at the periphery of the skin, and then a, an equivalent amount of vasal constriction going on at the gut. And you'll see then here in a second why there's multiple problems with that. And it turns out the, the epithelium of the gut is very sensitive to reduced oxygen delivery or hypoxia.
Dr. Lance Baumgard (19:24):
Picture's worth a thousand words. Now, this is the ileum of ileum of a heat stress pigs, but this is the thermal neutral, a li group where the ileum are long and slender. So this is a hallmark of a healthy intestinal barrier, integrity, and the ileum of the heat stress, you know, the villi even hard to distinguish so that the damage is clear. Now, interestingly, from a just sim just simply having a reduction in feed intake of only about 40% damages the gut, the VII becomes shortened and fatter. Okay? So I don't have time today to talk about how, how off feed events or inadequate feed intake and damage the gut as well, but it does. So remember, I I talked about trillions of, of, of microbes in the gut, and if they get in through the barrier of the gut, they'll stimulate the immune system.
Dr. Lance Baumgard (20:19):
Well, one of the things that's in the gut, it's called lipopolysaccharide. And in a normal human, there's well over a gram of it in, in the gut. So there's probably many grams of it in, in, in the gut of a, of a cow. And in LPS it's, it's made by gram-negative bacteria. It's out membrane component of gram-negative bacteria. It, if it infiltrates a barrier like a scratch in your hand or your gut, it's, it, it, it stimulates an immune response. And probably everyone on today's talk is familiar with being sick, right? You have reduced appetite, fever, muscle breakdown, you become lethargic, you get tired. So, so, so LPS is what we use in the laboratory to stimulate an immune response or try to model an immune, an immune response. Here's an over simplified cartoon of what your gut looks like. These are two enterocytes, and the enterocytes create and synthesize these proteins called tight junction proteins.
Dr. Lance Baumgard (21:20):
There's a red, where there's at least 50 different types of fight tight junction proteins. Now they're made obviously within the cell, but they're embedded on the lateral side, and they reach out and they make a physical connection with their neighboring cells, tight junction proteins, and, and create almost like a, a Velcro barrier, or almost like a zipper, for example. Essentially what it's doing is it's, it's a gate for during the, in this paracellular pathway that prevents LPS pathogens and other antigens from that are in the naturally in the lumen of the gut from getting in. Okay? But first, as it turns out, now we're learning more and more that any type of stress, even psychological stress, will cause these tight junction proteins to be pulled back into the cells that created them. They're still there, they're just not where they need to be.
Dr. Lance Baumgard (22:13):
And now this, you, you no longer have this physical barrier, and you get the infiltration of, of LPS and, and undoubtedly hundreds if not thousands of different types of antigens will, will get in. And remember, most of the animal's immune system resides in the gut. So if the immune system doesn't, if the local immune system does a good job you wouldn't even know that you've had a leaky gut. If you've had an infiltrating antigen, if the local immune system is unable to clear it, it travels via the portal blood to the liver. And the macrophages, the resonant macrophages in the liver, they're called cou for cells, will hopefully do a good job of detoxifying that, that arriving LP s if the liver's unable to handle all the LP s that it's arriving now, the, the endotoxin goes systemic and the animal starts experiencing endotoxemia, hell, it can even experience bacteremia.
Dr. Lance Baumgard (23:05):
So that what that means is that entire, that entire bacteria can seep through this para solia pathway, travel via the portal blood, and get through the liver and go systemic. Okay? So the effects of, of heat stress on, on the gut are very quickly. This is jugular vein, LPS. So on the x axis is time. And within two hours you see this noticeable increase in circling jugular vein. LPS. The reason why I'm emphasizing jugular vein is because obviously if you can pick up an increase in LPS, in the jugular vein, you're the, the local immune response of the gut has been overwhelmed, and so has the liver. Now, this, this, these animals are experiencing endotoxemia. And then not surprisingly, because you have this infiltration of antigens you, you're having an immune response. These are two acute phase proteins help binding protein and stream lymphoid a and day of a heat stress on the X axis.
Dr. Lance Baumgard (24:05):
So when there's heat stress, you get leaky gut, you have infiltration of, of antigens like LPS, and you end up getting, end up getting an immune response, okay? Pretty substantial immune response. So at this stage of the talk, there's the summary is that reduced feed intake only explains about 50% of the decrease in milk yield. There's a strange hyperemia. The liver's not responsible for the problem. It's making the glucose, the glucose is just simply not ending up in milk. There's leaky gut, there's an immune response. And in reality, the biological consequences of heat stress aren't much different than normal infection, okay? And, and at this stage of the top, we can't identify where this 400 grams of, of glucose has gone, so the gut becomes leaky, right? And, and there's a variety of different models that demonstrate that. And you're probably asking yourself, okay, what's the big deal?
Dr. Lance Baumgard (25:03):
What are the consequences of this? Right? So to, to answer that, we need to have a good feeling of what's going on with insulin. Why, why is there, there's a strange increase in circulating insulin during heat stress, and it happens incidentally, this also happens during infection, sepsis, eczema, and we can very nicely model this increase in insulin by infusing LPS. So what, what would be insulin's role during heat stress? Well, a, a good friend of mine when he was working with Tom Wilton, he, Bo Claire, was, was studying the consequences of, of me, me metabolic consequences of mastitis. This is Matt Waldron work from his postdoc. So they infused LPS up the teeth canal. At time zero, the cow gets a fever, completely stops eating, and approximately two hours later, there's this insulin surge, which is strange, right? It's, this is the animals got mastitis, severe mastitis, it's completely stopped eating. Why would the most anabolic hormone go up? Again, just a quick reminder, how important glucose is. It takes 72 grams of glucose to make one kilogram of milk. And if anything, reprioritizes the hierarchy of, of how glucose is used, it is gonna cost or has the potential to cost milk.
Dr. Lance Baumgard (26:26):
That leads us to a guy named Otto Warberg. Otto Warberg was a professor in Germany, and he receives the 1931 Nobel Prize for identifying a couple things. One is that immune cells prior to be, sorry, cancer cells prior to becoming cancerous can burn a variety of different fuels. But once they become cancerous, they, they initiate this thing where they, they switch from oxidative to phosphorylation, meaning they, they stop using the kreb cycle and they start generating their energy only from aortic glycolysis, which is an inefficient system. He, he also recognizes that immune cells are the same way. So immune cells before becoming activated by an antigen are quite metabolically flexible. They can burn a variety of different fuels, but once activated by antigen, their preference becomes glucose, and again, not through oxidative hospitalization, but through aortic glycolysis. And I'll show you the cartoon of that in a second.
Dr. Lance Baumgard (27:26):
And so he wins the 1931, no prize, 31 Nobel Prize. Three of his former PhD students go on to win Nobel prizes. One of 'em was Hans Kreb, and he was also good friends with Albert Einstein. So this is an amazing man. He was, he was influenced on, on, on science is going on over a dec or a century now. So the Warburg effect essentially just demonstrates that you have a, a resting immune cell could burn a, a variety of different fuels. Here it's shown glucose coming in, going through glycolysis, two py pyruvate molecules coming down to the TCA cycle or the Krebs cycle, and generating efficient quantities of a TP. This is an efficient process, but a slow lumbering process. Now, an activated immune, immune cell activated, for example, by LPS has a very rapid increase in need of energy. And so it, it no longer has the flexibility of burning different fuels, and it only wants glucose, and of course, it needs insulin to get this rapid increase in glucose or uptake of glucose.
Dr. Lance Baumgard (28:34):
So this is an, an, this is not anaerobic glycolysis like we all had to memorize in biochemistry. This is, this is an aerobic glycolysis that is induced by an immune cell to generate rapid quantities of, of a TP. The net result then is this carbon is exported from the immune cell as lactate. And, and this explains then why an animal that's sick or as in some type of infection, oftentimes has high levels of circulating lactate. Okay? So how much, right? How much glucose, remember it takes 72 grams of glucose to make one kilogram of milk. Well, this has been difficult because it's, it's, it's very hard to isolate and localize the immune system. Every tissue has resonant immune, even the brain has a resonant immune cells. And to make matters worse, it, it migrates, right? It might, if you got a infection in your big toe, your immune system will mi migrate to the big pill, so you can't isolate it.
Dr. Lance Baumgard (29:37):
So attempting to quantify the glucose needs of an immune system requires you to do that at the organismal level. So we, we initiated this thing called an LPSU glycemic clamp, and it's a fancy word for essentially just infusing glucose. We give glucose at, or sorry, we give LPS at times zero. There's a couple hours of hyperglycemia. And this is, this hyperglycemia is because the liver's glucose output increases muscle and adipose tissue stop using glucose, peripheral insulin resistance. And these three systems outweigh immune system glucose utilization. But once the immune system gets fully engaged, and almost all immune cells do this, by the way, almost all leukocytes now their glucose utilization will outweigh the body's strategy to provide glucose for the immune system and they become hypoglycemic. Okay? So we kind of thought, well, what if we just, we start infusing glucose the second she becomes hypoglycemic?
Dr. Lance Baumgard (30:43):
Could we, could we get a, could we get a proxy of overall glucose use? So graduate student injects LPS on into the jugular vein, we take blood samples, we measure the blood glucose levels, and as soon as she becomes hypoglycemic, we init, we start infusing glucose. We do this for 12 hours, we subtract off the controls and it's approximately a thousand grams of glucose, a kilogram of glucose in a 12 hour timeframe extrapolated to a day. We're talking two kilos, two kilograms of glucose is an enormous amount of of energy, right? You're, here's a, there's a 1.81 kilograms of, of, of, of table sugar. And so this is an enormous amount of, of utilization of energy. And we've done this now in a variety, different species. And, and when you, when you place the data on a metabolic body weight basis, it, I don't think it's surprising how similar then these, these, these data are about approximately a gram of glucose per kilogram of metabolic body weight per hour.
Dr. Lance Baumgard (31:53):
So remember back earlier when I said we, you know, we had heat stress cows we're secreting about 400 grams less carbohydrates per day than the para fed controls. Well, right? The cow gets heat stress, it gets leaky gut, leaky gut stimulates immune system. The immune system now is the number one priority. And and they start, and the immune system starts to utilize glucose, and the mammogram is just no longer high in the totem pole. Okay? So what can we do about it, right? What, what can the feed on animal health industry do to, to fix leaky gut and, and, and heat stress? Well, there are a variety of different targets. Increasing feed intake, direct actions at the intestine, and we will talk more about some of these diet dietary strategies here in a second. But by far the biggest impact a producer can do is heat stress abatement, right?
Dr. Lance Baumgard (32:48):
Physically modifying the, the environment is, is by far, I can't emphasize that enough. The best investment of money, and I'm, I've just kinda listed them here, shade fans, soakers and misters. And, and so, so what are the benefits from investing in cooling? Well, I think I, I would assume most people have a good, fairly good feel for this already, but obviously from improved production efficiency and profitability summer fertility is a huge issue. Probably 50% of the decrease in in the economic consequences of heat stress are, are, are poor reproduction, welfare, health sustainability, right? And so what would the priorities of, of heat stress be? Well, I'll show you here in the next slide, but solar, radiate solar radiation is, is incredibly intensive. I'll just show you some data to, to prove that. I think most people know that in the second then would be to utilize evaporative cooling of course, while incorporating fans.
Dr. Lance Baumgard (33:53):
So this is very old data now, right? 70, 70 years. But this is just simply looking at black dirt surface temperature. This is data from Nebraska, black dirt surface temperature during the middle of July day. So in the sun, no shade at four o'clock in the afternoon, the, the temperature, the black dirt temperature was 153 degrees. And just simply providing five minutes of shade will markedly reduce the temperature of that ground. So the emphasis here, I'm just trying to show you, is the power of shade, right? I think everyone probably has familiarity with that already, but just simply providing a small amount of shade can markedly reduce the, the thermal load on, on an animal.
Dr. Lance Baumgard (34:48):
The other one I just want to talk about quickly is evaporation. And I, I don't want to freak you out and remind you about physics, but the amount of energy needed to evaporate water is enormous, right? 540 calories to evaporate a gram of water going from a hundred degrees Celsius into steam. Well, this explains why steam burns are so, are so dangerous, right? Because there's so much more energy in the steam than there is in the hot water. And so, so let's, well incidentally, there's also energy liberated during condensation. So the same thing is true going both direction, one evaporating or vaporizing water. And the other one is, is condensation. And we'll give you examples of that both here in a second. But, so the evaporation is a cooling process. I've already talked about the quantity of energy needed to evaporate water.
Dr. Lance Baumgard (35:47):
And this explains then a variety of, of things that we're all have familiarity with, right? When you get out of a swimming pool, it might be a hundred degrees and you still get chilly. Or when you get out of your shower, before you got in your shower, you weren't cold, but now when you're coming out of the shower, you're cold. Well, why is that? It? It's because when, when you're wet and you're walking out of now of the, of the pool or your shower, the water that's on your skin evaporates, and the energy required to evaporate that water is being, is coming from the thermal energy on your body or in your body. So the water evaporates, the energy required to make it evaporate is coming out of you. So you, that's, that evaporating water is literally sucking energy, thermal energy out of your body.
Dr. Lance Baumgard (36:37):
Okay? this also then explains why it's warmer to stay in the shower, right? You get outta the shower, I mean, you shut off the shower. Why is it warm inside the shower? Well, because that water that was vaporizing during your shower, it's now starting to condense and condensing liberates heat, right? So we talked about the opposite, right? Con condensing water. Liberates heat. That's why it stays warm inside your shower even after you shut off the water. And when you get out, that water's evaporating off your skin. That's why you get cold. Others examples are, for example, blowing on hot coffee. What you're doing when you're blowing on hot coffee is, is changing the gradient of the temperature, allowing that the energy then to, to, to vaporize that water is coming from the thermal energy in the coffee. So when you blow on water and you see the steam, or sorry, hot, hot coffee, and you see the steam or the vapor leaving the coffee, the energy required to vaporize that is coming from the thermal energy of the coffee and the temperature of the coffee then goes down.
Dr. Lance Baumgard (37:44):
And I'm, I'm emphasizing this everyone, 'cause I think everyone, everyone has familiarity with the power powered evaporative cooling. Sometimes you just don't wrap your head around or think about, think about it. So there's three ways of Eva to utilize evaporative cooling is to cool the cow. And in this particular strategy, you're literally putting water on, on the cow's skin and evaporating it off, right? And again, the evaporation of that water on the surface of the cow, the, the, the energy required for that is coming from the body temperature of the cow and the cows becomes cool, cooling the air. This is a, a strategy that's oftentimes utilized in, in more arid climates like Arizona, right? Where you the producers there will, will, will, will introduce very tall, very small droplets of water around the cow that wa that that water will evaporate hopefully before it hits the ground. And again, the energy required to evaporate that droplet of water is, is coming from the air temperature in this particular example. And now the air temperature has gone down because the energy has gone into evaporating that, or vaporizing that water or some type of combination of, of, of the two.
Dr. Lance Baumgard (39:01):
I got this slide from John Smith gave the late John Smith gave me this slide, and a couple, actually a couple of the others priorities to reduce heat stress. Obviously cows will increase their water consumption when hot to provide shade. We, we talked about why that is. And importantly, don't forget about the dry cows. I'll show you some data here in a second about dry cow cooling utilize evaporative cooling and even in relatively humid climates like Iowa and the Northeast, the northwest evaporative cooling is, remains, remains effective at not clearly as effective as, as in more arid climates or low humidity comets, but it remains effective. Fans are, are, can utilize to to dissipate heat and also to increase evaporative cooling. Minimizing distance of the parlor holding pen is almost always the spot on areas where cows get the hottest, improve ventilation and where to do it.
Dr. Lance Baumgard (40:06):
You know, long story short, if you can afford it everywhere, right? If you can, so the summary of heat stress abatement providing good shade utilizing evaporative cooling more water, the better. And, and the, the, the frustration I get from, I can hear the frustration oftentimes from producers, well, I have to have to get rid of this water. Now, part of this evaporative cooling is utilizing, is managing the evaporative cooling to, to try to minimize wasting water. But, and again, also, I don't know, you know, what the cost of water is in, in everyone's systems, but don't forget about the dry cows. I'll show you data here in a second and try to measure it. Where if you're gonna invest in cooling, try to get some metrics that allow you to, to, to recognize that your investment's paying off. So this is some, some data from Dennis Armstrong who is on faculty at University of Arizona.
Dr. Lance Baumgard (41:13):
When I first got there, and he's a legend in in heat stress abatement strategies. He was working with dairy farms in Saudi Arabia. And so they, here let me, three different dairy farms over here in the far left column. And they were heat stressing. There were cooling dry cows or not. That's the only treatment. Okay? So the, in the dry period cows are either cooled with shade, evaporative cooling, or they weren't. And then once they calved, all cows were cooled. And these are just different metrics of, of reproduction and in, in all metrics and in all three dairies, the cows that were cooled, pre calving had improved metrics of, of reproduction. And, and on the far right, I'm sorry, is is calling because of reproductive purposes. So, so clearly the, the, the benefits of cooling a dry cow extend far into lactation.
Dr. Lance Baumgard (42:17):
Bob Cowler and others were also looking at the biology of this at the University of Florida and, and Jeff Dahl and those guys are, are also extending that. So there are mark improvements, future improvements. We're talking 60 to a hundred days following that cooling on, on reproduction. So, you know, I'm a Star Wars guy, but I, I just hope now everyone has a, a good, a good feeling for just how powerful evaporative cooling can be. Even in climates that are, that are relatively human evaporative cooling, if managed correctly, is, is still a very good use of, of invested money.
Dr. Lance Baumgard (43:01):
Some di some management strategies I already talked about reducing the distance from, from the, from the, from the parlor. The holding pen is where cows get packed in like sardines, they become stressed. Consider exit lane cooling. I think that's a good strategy. Try not to lock up during the middle of the day. A good friend of mine short feeds. So if, if you can know when a heat stress is, heat wave is coming short, the cows about 5% of feed on the day before, and then the on the day of heatwave, they have a, they're aggressively eating. That also requires quite a bit of management feeding later in the night, early in the morning, push up feet often, you know, if you put your hand in the feed and it's hot, they're not gonna eat it. And I understand the producer's reluctance to throw it away, but you know, hot moldy feed, fermenting feed is not, they're not gonna eat it.
Dr. Lance Baumgard (44:02):
Try to avoid vaccinations during the middle of the day. Of course, that's vaccinations are accompanied by a small fe oil response and at least provide shades for the, for the dry cows, if not some evaporative cooling. So dietary strategies, right? These are mostly I think theoretical. I have a hard time studying these at the university, but low heat increment diets, trying to save your best forge for the warm summer months, fat I i, there're surprisingly not as much research on dietary fat as you'd think, but most of them do show some type of improvement of increasing fat content of the diet. And of course that's because the digesting absorption of fat is, is accompanied with low amounts of heat, a balanced amino acid profile. And with regards to supplements, I think there's a variety of things and different strategies, right? I I haven't even talked about how heat stress causes room acidosis, but modifying rumen ru environment supplements aimed at improving gut integrity, feed intake stimulation, immune modulation we want, wanna talk about today is the vasodilators.
Dr. Lance Baumgard (45:13):
Okay? When I was at Arizona Bob Collier was leading an effort looking at how nice and affected heat stress and dairy cows. And his, his PhD student was rosemary resemble. And so the first experiment they looked at, I think this was 12 grams of niacin a day, and this is vaginal temperatures of, of heat stress cows when they were, and the controls were in black, and when they were fed the niacin it was in the open gr open, gray, open this open gray, I don't know how these call this. Anyway, this is, these are the animals that were fed the niacin. So there was a substantial increase, sorry, decrease in, in body temperature when they were fed the, the niacin. And Bob did another experiment looking at a dose response. And that particular experiment did, didn't reproduce the, the body temperature data, but they, they did see a linear increase in, in water consumption with increasing doses of, of, of niacin. And then Bob did another ex experiment looking at the molecular consequences of, of, of beane and niacin. And interestingly enough and I'm, I'm not going to get through all the, the heat shock proteins in, in all the nuts and bolts of Bob's paper, but what, what I'm trying to demonstrate is that the effects of niacin on the cellular machinery that regulate the heat shock's response are pretty, are pretty significant. Okay.
Dr. Lance Baumgard (46:49):
So back to the gut, I think, I think leaky gut can explain a variety of things. And again, I didn't have time to talk about ketosis and offbeat events and fatty liver, but I think there's a variety of things and in anima agriculture associated with leaky gut, and in, in large part, it's just due to stress. So the stress umbrella that we've been, we've been developing in, in our group where you have these, these different stressors and causing reduced feed intake. And this reduced feed intake is just only part of the problem. The other part is this leaky gut induced immune activation and then nutrients being utilized that would otherwise have gone to making of milk or a fetus or muscle. Okay?
Dr. Lance Baumgard (47:40):
So near in the end here, heat stress costs it decreases almost every metric of productivity in profitability. And it's not just a, you know, large or a small dairy farmer issue. It costs everyone in the industry. Reduced feed intake is only a small portion of the problem. There's this heat induced leaky gut, and essentially the biological consequences of heat stress are, are incredibly similar to just simply other immune activations, mastitis, metritis, et cetera. From a dairy producers perspective, heat stress abatement is, is by far the, should be their biggest priority. And once they've invested in then these infrastructural changes, dietary strategies I think are also a good strategy to minimize negative consequences of heat stress. The USDA has been very good to us, and this is my team. I have a team of rock stars and they do all the work and, and collaborators. So I, I hope, I hope you found the hour here useful and I'm happy to take any questions if you have them.
Balchem (48:56):
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Scott Sorrell (49:22):
Dr. Bomgar our first question is, if you were implementing a cooling system on a dairy and you could only do one project at a time, where would you put your first priority?
Dr. Lance Baumgard (49:38):
Yeah, so I'm gonna, you know, I've heard, I've heard you know, Bob Collier and John Smith been asked this question many times, and I'm just gonna essentially regurgitate what, what I've heard them respond. You know, first is, is making sure there's plenty of water access to clean water, and this is probably the cheapest thing you could do is just throw the grandkids out and make sure you clean the water tanks right. Second one would be shade preventing that solar radiation. And then the third is utilizing evaporative cooling with fans.
Scott Sorrell (50:15):
Right? Excellent. Next question with regard to heat stress and LPS, how significant does a bout of heat stress need to be to initiate the response? For example, if a group of cows experience heat stress during the day, but it cools off at night, will that initiate leaky gut or does it require a more prolonged exposure?
Dr. Lance Baumgard (50:36):
Yeah, that's a great question and I'm, I'm gonna, I'm gonna allow productivity to help guide my, my, my response here. If a cow is able to cool off that night and and eliminate all the heat that she was accumulating during the day the effects on, on, on milk yields seem to be pretty small, and all you need to do is go to visit some dairy farms in, in New Mexico versus Arizona and, and look at the infrastructures and, and, and the amount of money invested into different dairies to, to know that, right? And so it cools down much better in, in, in New Mexico than it does Arizona. So yeah, there the question's hard to answer. You know, how many hours of accumulated heat is required, because of course you have cows that are acclimated and not blah, blah, blah, but if they're able to get rid of that heat and start the next day with their body temperature back to normal, they, they seem to really tolerate heat stress pretty well. So the amount of heat required to cause this, this leaky gut must be some type of like you know, 24 hours, 36 hours. But it's a good question.
Scott Sorrell (51:55):
All right. Very well, let me see if I can get the gist of this next question. Is there a level of leaky gut question mark, for instance, a level where only toxin can access the bloodstream and a level where bacteria access the bloodstream?
Dr. Lance Baumgard (52:10):
That's a great question, and I suspect there is a continuum, right? And where the early stages of impaired intestinal integrity, you probably get the, the small products of, of bacteria like LPS and other antigens, and then as the gut becomes more severely injured and the paracellular pathways become even more and more open, then you'll, you'll get larger molecules like entire bacteria getting in. It's a great question. I don't, I, I'm unable to give you a, a specific time or heat load, but I suspect there's that continuum where it's first end LPS endotoxin and then eventually whole bacteria.
Scott Sorrell (52:59):
All right, thank you. Next question. Where do you think the gut gets most of its energy from oxidation of VFAs? If so, can we feed the rumen better to potentially preserve gut function?
Dr. Lance Baumgard (53:15):
Yeah, great question. And I think there's a again, there's a of course butyrate is a key e energetic substrate for the rumen and for a large intestine butyrate's contribution as an energetic fuel source for the small intestine, I think would probably be less than these other two segments. Glutamate, glutamine and, and glucose are also sources of energy for the small intestine. You know, I, I think there's strategies at trying to maximize butyrates contribution to energetics in the large intestine. It's a hard question and you're probably getting tired of me saying, I don't know,
Scott Sorrell (54:33):
Alright, I think we've got time here for a couple more, Lance. Next question is valuable information regarding ev energy metabolism and heat stress animals as a primary nutrient amino acids metabolism also can be changed in heat stressed animals. Do you have any data regarding the amino acids composition change changes in the physiological status of heat stressed animals?
Dr. Lance Baumgard (55:06):
No, not really. I'm gonna calculate from, from other species. So the immune system has a huge increase in glucose metabolism use, but it also has a huge increase in amino acid requirement as well. And the issue with amino acid metabolism during heat stress is that, so I didn't talk about the mobilization of skeletal muscle during an immune response, but they do. Animals will mobilize, adipose, or sorry, skeletal muscle, but the amino acid profile of skeletal muscle is different than that of the acute phase proteins. And what, that's one of the big reasons why the skeletal muscle is being mobilized to provide amino acids to the liver, for the liver to utilize those amino acids to make acute phase proteins. But the amino acid profile is different between the two. So skeletal muscle is mobilized in excess of what's needed to make the acute phase protein. That's why blood re nitrogen markedly goes up. So I, I think there's opportunities for us as a, as nutritionist to to get a better understanding and, and be able to predict what that amino acid profile is and then thus feed to meet those requirements. And that's not just a heat stress thing, I think it's also a transition period transition period issue as well.
Scott Sorrell (56:42):
All right. I'm mindful of our time here and I think we have time for one more question. I do want to tell everyone that if your question was not answered today, we will be forwarding these to Dr. Baumgard and he will answer them and then we'll make them available on our website bal him nh.com/real science. So last question. How many days slash weeks before the first heat wave arrives should we start feeding additives to help heat dissipation?
Dr. Lance Baumgard (57:13):
Well, I think you definitely want you know, from a nutrition perspective to preemptively, preemptively get there before the heat wave gets there. So if you're able to, it depends upon which supplement you're talking about, probably, and you know, the, the ball cam scientists probably have a better idea of how long CIN needs to be fed before you get the vasodilation effect. Depending upon the supplement, if it's a, if it's a gut issue, you know, some, I would think you, you you wanna have it preloaded before the heat arrives. Oh, yeah, I don't know the week five days. The problem is accurately predicting heat waves is, is difficult unless you live in Arizona where it's hot all summer, Texas, Florida but in the Midwest, northeast, of course we have heat waves. So it also depends upon the cost of the supplement and everything. So I, I'm not able to give you a good answer. In fact, I don't think I've answered a single question yet. I apologize for that.
Scott Sorrell (58:25):
You've been awesome today Dr. Bomgar, and I want to thank you and I wanna thank everybody for attending today's webinar on behalf of Chem and Dr. Bomgar, thank you for joining us today.
Balchem (58:36):
We'd love to hear your comments or ideas for topics and guests. So please reach out via email@anh.marketing at chem.com with any suggestions and we'll work hard to add them to the schedule. Don't forget to leave a five star rating on your way out. You can request your Real Science Exchange t-shirt in just a few easy steps, just like or subscribe to the Real Science Exchange. And send us a screenshot along with your address and t-shirt size to anh.marketing at balchem.com. Balchems real science lecture series of webinars takes place on the first Tuesday of every month with the top research and nutrition topics that will impact your business. We also include small ruminant, monogastric, and companion animal focused topics throughout the year. Visit balchem.com/realscience to see the upcoming topics and to register for future webinars. You can also access past webinars and search for the topics most important to you.