Hello, everyone. My name is Lotaro Rosto. I'm a faculty in the Department of Animal and Dairy Sciences at the University of Wisconsin.

And today I'm gonna talk about some of the emerging topics that we can try to implement at a farm level to try to improve calf health and development and hopefully try not only to improve incidence or reduce incidence of disease in the pre-weaning period, but hopefully try to programme those animals so that they can be healthier throughout their productive lifespan as well. So, We all know that raising successful raising he successfully, it's a key aspect to the economical sustainability of any dairy operation. Regardless if you're in Europe, in North America, and South America, that, statement always holds true and at least in here in the US, Depending on the year, but the rearing cost represents roughly close to 20% of the cost of any dairy operation, and that's gonna be mainly dictated by the size of the, the scale of the operation, how much is spent in it, but like close to that to give you a, a good perspective on how expensive it is to rearing those animals that are going to be the next generation of cows in our herd, in a.

To your point, time frame. So there are several factors of the current veering system that affects the development programming. Of these haiers on, on the way that we manage them, especially in early life, they're going to affect the health and growth rates in the pre-ing period, but not only that, but also it's been shown they can have a big impact on milk production during first lactation and also in second lactation.

And it's also, which, and this is, this is very interesting. It also can affect the productive lifespan of those animals, making it shorter when we make decisions that goes against the successful developmental programming of those animals. .

So kind of what my lab do is try to work on developing strategies to improve long-term health outcomes on these animals, but first we need to get a better understanding of what are some of the biological, physiological, and molecular mechanisms that are at play that modulate that interplay between the host and the environment that that animal is raised in. So with that, we are trying to see how different nutritional and management strategies and factors can influence specifically the development of the immune system of these animals in early life and then how that can have an impact on disease incidence or disease resistance. So, despite some significant advancements that has been done in the last couple of years, in how calves are managed in the pre-weaning period, there are still significant challenges.

At least in the US, in, in Canada, mortality rates are still high, between 5 to 8%, and morbidity, it depends on the study and the condition, but it ranges all the way around 30 to 45%. So which that means that almost 50% of your calf population. During the window of the 1st 2 months of life, at least half of them, they're gonna get sick.

Here on the right, we have a graph that shows the incidence of the disease during the pre-weaning period based on age on weeks and we see there's a big spike on diarrhoea cases, which is the most common morbidity for calves during this, during this period. And there's a window between the 1st and and 4th week of life, typically peaking around the 2nd or 3rd week of life. Also, we have respiratory disease and there are some other common comorbidities in there, but the most common ones, at least what we observe is diarrhoea and respiratory disorders.

And one of the reasons for that is the mismatch between the biology of these animals and how they are raised on commercial farms. Calves, when they are born, they're born what is called immunologically naive, and there is no transfer of immunoglobulins through the placenta on these animals in cattle as compared to humans where humans will get born and they'll have circulating high circulating concentrations of immunoglobulins that have been transferred through placenta from their mothers. In cattle that doesn't happen, the placenta.

Doesn't allow for the transfer of immunoglobulins, and all the immunoglobulins that they receive, they receive them exclusively from corruption. And there is only a short window of time that they can absorb those immunoglobulins and those immunoglobulins can enter systemic circulation and effectively protect the calf against disease. So, Colossum and you'll see, we'll discuss this in more detail during the, the entire presentation, but it's the most important determining factor in In promoting calf health and protecting against disease during the preing period.

And then when these calves starts getting older, that immune system is going to gradually continue to mature and being able to respond better to environmental pathogens, respond better to vaccination strategies. But as I said, the cat in this period of time, Depends exclusively on the transfer of passive immunity from caution. So it's very, very important that we can hone our management protocols for culture feeding, so that we can support the health and welfare of these animals during this, during this particular period.

So I want to show you this because I'll use it later to reemphasize a statement that I'm gonna, that I'm gonna be making about the use of antimicrobials for treatment of diarrhoea and the use of preventative antimicrobials for the prevention of diarrhoea. As you see here in this graph, we have the most prevalent pathogens that are responsible for causing disease in calves and the typical incidence. What you first see here is that the main ones or the most prevalent ones, at least on these conditions, and it is actually data that comes from the UK are not, are not from bacterial origin.

They are viral, they are parasitic. And there, and also coccydium. And also what it's interesting is that the majority of diarrhoea cases, the etiological factors that are involved here are typically more than one.

So we always talk about call infections or mixed infections. So, treatments with antimicrobials for diarrhoea, they are not. And They're not very successful.

They, they, they play a role and they are important for treating bacterial origins from, from bacterial origin. But there's always, some lack of effect because of this, that there's mixed infections and then, in addition to, to bacteria, you have You have viral and parasitic infections that play a role in there as well. So, I think before we try to discuss how we can treat diarrhoea better or how we can prevent diarrhoea, we need to understand how diarrhoea happens in the first place and what are some of the symptoms that we have to try to alleviate on the cough.

So, diarrhoea, the main negative impact that diarrhoea has on calves is the, is the loss of electrolytes. Through, unregulated, Process of water lost when you have particular pathogen that is trying to, that is trying to infect the host in this case in the calf, and the immune system responds promoting inflammation. That inflammation promotes pull of electrolytes and water from in the calf into the lumen epithelium.

And that typically results in two things. There's a loss of absorption from of electrolytes and water from the feed, and it's also there's a loss of electrolytes and water from the host, as a result of the progression of the infection. So the first thing we have to try to do in these scenarios is to replenish those electrolytes.

The animal is losing. By using electrolytes. And the second thing we have to try to do in these cases is to try to reduce.

the impact that inflammation has on the tissue of the intestine. So the second thing, that has proved very successful, for us is the use of anti, anti-inflammatory drugs. .

In Canada, we could use meloxicam. In the US, meloxicam is not allowed to be used for treatment of diarrhoea and calves. I don't know what the scenario is in the UK, but the point is that we have very successful responses from the calf with diarrhoea when we treat them with a combination of replenishment of electrolytes with electro therapy plus anti-inflammatory drugs.

Yeah, and the reason for that is that we are targeting the specific, Targeting the, the specific responses of the host, and we're trying to alleviate that. And of course, if this is a b bacterial origin, diarrhoea, if there's a bacteria that are causing this diarrhoea problem, we would have to try to treat it with, with antibiotics. But I think it is important to understand what are the theology, what are the causes that are causing the diarrhoea in our forms.

So it's important that we try to routinely try to measure, What pathogens are causing that and the most easy way of doing that, you can submit samples to diagnostic veterinary labs to tell you what are the most prevalent pathogens that you have on farm and to try to work with vets. At your facilities to try to come up with strategies that specifically target the pathogens that you have and, and try to reduce this incidents in a more targeted approach instead of using just a blanket treatment with antibiotics. And the reason I say this is, we know, at least in the US at least 75% of calves.

In a dairy farm are treated with antibiotics for diarrhoea. And in Canada, the scenario, it's, it's, it's, it's much lower, but, but it's still, but it's still prevalent. And the point I'm trying to make here is that antibiotics have a role, and they play a very important role in treating diarrhoea cases.

But we need to use a better strategy to target those cases where actually antibiotics are needed and for other circumstances there are other And there are, there are other protocols that we can, that we can use to try to alleviate this. So Another, another factor I want to, to discuss is on farms, at least here in the US it's still very common to use prophylactic antibiotics, mainly neomycin and oxytetracycline. So we did a study that we, we're trying to understand what was the effects, what was the actual benefit of feeding neomycin, which is the most prevalent prophylactic antimicrobial in Animal performance, measure on growth rates, in incidence of disease, measure as faecal scores, and also we look at incidence of respiratory disorders, which is not in here, but we also look into that.

So, and, and the treatments in here are short term are 14 days of feeding neomycin in the medical replacer. Long term, it's feeding of neomycin for 28 days and then we had a control that, that dog was not medicated. We asked the question, What's the impact of medicated mplars in these parameters.

So when we look at average daily gain, calves that were fed either neomycin for either 14 days or for 28 days, there was no improvement on animal performance, at least measure as average daily gain, . There was only a small reduction on faecal scores, which it would measures the faecal consistency. But actually when we look at calves, when they develop diarrhoea, how long it would take them to get the first diarrhoea.

Actually, there's no difference in there. And also, the time it takes to resolve a diarrhoea issue was also not significantly different between treatments. So, and, and, and in addition to that, there was no difference on respiratory disorders between, between treatments in here.

So, what we show with this study is that at least on the conditions we did the study, Use of neomycin prophylactic for prevention of disease was not very successful. And in addition to that, we know that excessive use of antibiotics can have unintended consequences on the development of the animal and that has to do with how this can impact the intestinal microbiota, and then we now have a much better understanding of the beneficial roles those intestinal microbes have on programming developing on the, on the host, in this case, in the calf. .

And then using this kind of blanket treatments can have an effect reducing the, the abundance of beneficial microbes that play a very important role in early life. So, because of this, we now see epidemiological studies that they look how much antimicrobial treatments are delivered to calves in, in, in early life in the pre-weaning period and how and what are the long-term consequences of that on those animals that are treated for more, with more antimicrobials. So we know now that calves treated with antimicrobials in the pre-weaning period, they have lower conception rates when they reach the productive herds.

They have increased time to first calving, so it takes them longer to calve probably because they get pregnant less. And also they have increased risk of, of cooling them from the herd for several disease or metabolic disorders. And they also produce less milk.

So now, An important point here is that at least at this point, we don't know exactly if this is caused because of additional use of antimicrobials on this specific group of calves or if it's because those animals are more sick, therefore, they're growing less and they develop less compared to their counterparts, and then that is the thing that is driving These negative outcomes, OK? But that's one of the main areas that my lab is dedicated to, to try to understand what's the role of antibiotics in early life and, and, and how that specifically might be programmed the animal to be less productive and more prone to becoming sick in later stages of lactation, in later stages of, of development. So Another study from a colleague from Michigan State, they also did the same thing using records from the, the dairy herd from the University of Michigan, and they followed 2200 animals from birth to the end of the first lactation, and they divided them based on antibiotic treatments and what they saw is that those animals, they grow less during the pre-weaning period.

They They have reduced conception rates as well, around 5% less, and they also produce less milk on the first lactation. So what I'm trying to make a point here is that we need to be more cognizant of the treatment decisions that we make on these animals in early life and try to explore different alternatives because we might be programming. These animals to be less productive.

And then on top of that, antimicro treatments are expensive or, or treatments are expensive. In the pre-union period, it adds to the cost of rearing and raising those heifers, and also those heifers are not going to pay off the way that they should, we are reducing the, the return of investment that we're putting on those animals. In addition to that, in that study with neomycin, we look at how neomycin was affecting the total diversity of a microorganisms in the gut.

So, I, these are just indexes that measure different components of microbial diversity. The only take home that I want you to take from this, the point that I want you to take from this is that feeding of these antimicrobial prophylactically on those calves were the reducing the microbial diversity and microbial diversity, especially in early life, is very important. Because, microbial presence in the gut, promotes that gut and that immune system to develop and, and, and, and produce an epithelial barrier that is much more, much stronger and then an immune system that is much More able to respond later on against disease.

So, reduction of diversity actually has a negative consequence on programming that proper immune development of these animals. And that's what we saw when we were feeding this. And in regard to that, we look at how well the barrier function of the intestine was working.

So, for those of you that are not very familiar with this, the intestine, it's conformed of just one layer of epithelial cells that is covered with mucus. And these epithelial cells, they are tightly attached to each other and form a, a tight monolayer forming what is called in the intestinal barrier. So these, these cells, these enterocytes, they control.

Very well what comes in the gut and what has to stay outside. So typically, it allows for flow of nutrients and water and electrolytes, but it doesn't allow any external microorganisms to come through. But for this to be able to happen, then this epithelial barrier has to be Very tightly controlled and, and all these certain factors can come, come in.

When there's inflammation there or when there is a specific problem that doesn't allow for this to function properly, then you can have gaps in between the cells and that creates that creates a channel where other molecules can be Coming through in a process that is not controlled by those epithelial cells. And that can actually be a cause or drive further inflammation or actually drive infection. The way that we can measure this is by using Markers for intestinal permeability.

In this case, we use chromium EDTA and what we do is we feed these markers to the animal. And then we measure them in blood. So, the higher the concentration of these markers is in blood, the less And the, the more permeable this cut is because these markers, this small shouldn't go through if the viral function is functioning properly.

So, in this case, when we feed neomycin for 14 or, or 28 days, we saw that these animals that were receiving these antimicrobials prophylactically, they had an increase on intestinal permeability. I see here as the increase of chromium ADTA over time on those blood samples that we were taking. After, after we feed it.

So at, at 0 hours we dose those markers to the animals and then every 2 hours for 10 hours we do measure in blood the concentration, the rate of appearance, OK? And what we think here, it's what, what's happening is that reduction of microbial diversity is actually reducing the development of this viral function on these caves in early life, and it's actually promoting the gut to become more leaky. So, we know from human data, That the intestinal immune system is the largest human compartment in the body.

And colonisation with mucosal surfaces, it's, with microorganisms is critical for proper immune development of this immune system, having an impact longer term, not only of how that immune system behaves locally, at the gut level, at the mucosal level, but also at a systemic level. And there are several factors that can detrimentally affect this process. And one of the main ones is use of antibiotics during this early, early period.

And this is called this biosis, and then this biosis can have a lasting effects on how the immune system behaves and reacts later on in life because basically during that early stage where the immune system is not, is not highly responsive, it's actually being trained. To recognise what's friend from foe and to recognise what's a commensal microorganism from the gut to was actually a pathogen in the gut. So, when you disrupt this normal process, you can have lasting implications on how that immune system behaves.

So, What about the calf? What happens in our commercial scenarios with this, with these animal models. So the pre-weaning period, as I already mentioned and emphasise, is one of the most challenging stages of the life of these animals based on incidence of disease.

We see high rates of morbidity and pressure of disease. We use, in my opinion, excessive amounts of antimicrobials. And in addition to that, and that's, unfortunately something that is still very prevalent in North America is the use of milk.

So milk from cows that have been treated for a specific disease, it's sometimes it's fed to these calves and you have to wonder, those antimicrobial residues. That are in there, those high somatic cells, and also some potential pathogens, how that can be affecting calf health, not only in the premium period, but then based on these mechanisms that are mentioned, how that can affect animal health longer term. And We even seen studies when waste milk, even waste milk when it's pasteurised.

You can still see an effect on, on, on, on the calf. And for example, in this case, this is a recent study from 2022 where researchers fed either milk replacer, they fed a combination of waste milk with milk laser, fifty-fifty, or waste milk entirely, and this waste milk was actually pasteurised and then they looked at they looked at incidents of diarrhoea and then treatment with antibiotics or with electrolyte therapy. So actually calves that received waste milk had higher faecal scores.

And they also had more days. With abnormal faecal scores. Which is pretty interesting.

And in addition to that, animals that receive waste milk actually especially in the fifty-fifty mix, they were treated with more electrolytic therapy compared to the control. Forgot to make the animations, but waste milk feeding seems to increase severity of diarrhoea cases. Again, at least in this scenario.

So, what I typically recommend producers is in addition to use this data as food for thoughts is to try on your farms. If you're feeding waste milk on your farm, try to have a group that you either feed them, feed the milk replacer. Or that you feed them whole milk and see how those animals do compared to the ones that you're doing with milk and then do your decision, inform your decision based on actual data that is coming from your farm.

So How do we think that we can try to do better in this, in these circumstances? So, coloss feeding, as I mentioned at the beginning, it's probably one of the most impactful ways you can use to try to reduce overall incidence of disease on your farm. So We have 4 main things that we look when talking about Colossum.

The first one is quality. We are trying to ensure that colossian has at least 50 grammes of IgG in it per litre. The way you can measure this is with a BRICS refractometer.

Typically measured in bricks. We're looking at bricks. That is higher than 22.

Which which is going to be equivalent of these 50 grammes of IgG per litre. So you have to start there, huh. In terms of quantity, We're trying to feed at least 200 grammes of IgG in the first feeding.

Which typically equates to close to 8 to 10% of the body weight of that calf, we need to feed colossum. So if an animal weighs 40 kilogrammes at birth, you should be feeding that calf between 3.5 and 4 litres of colossum that has at least a bricks of 2022.

In addition to that, we also have to feed it as early or as fast as possible. Ideal would be within 2 hours after birth, but within 6 is acceptable. But the point we try to make in here is that the fastest you can deliver that coloss and those IgGs to the calf, the better it's going to be.

And in addition to that, feeding colossum that is clean, so that you can maintain good hygiene throughout the process of collection of that colossum, then when you're bo bottling it and then how you're feeding it. So it's important that you keep the bottles pretty clean. If you're going to tube colossum, that your tubes are also clean and then you change the tube routinely to avoid contaminations.

In the past 10 years ago, we would talk about successful passive immunity. Is when cows had in circulation more than 10 grammes of IgG per litre. That's what we used to consider, successful passage transfer.

But then in 2020, there was a paper that was published that used a lot of data comparing incidence of disease on caps on the preunit period compared to how much IGG they had in circulation. So based on that, they developed new Recommendations for what we should be considering a successful passive transfer of immunity. So based on that, they make a theories now that go from excellent to bad and So, what I'm trying to make a point here is that we should be aiming for much higher serum IgG levels on these calves, then we can also measure using a BRICS refractometer to measure total protein, serum total protein in circulation.

And I invite you to look for this paper that has the equivalent of IGG based on total protein and also based Some bricks. So depending on how you do on the farm, you can do it based on bricks, so you can do it based on total protein. But the point here is we should be aiming for higher amounts of iogen circulation of these animals.

This is an electron microscopy image from an animal that was not fed colossum compared to one that was fat colossum and these animals were dissected at 24 hours of age. And then in this image on the left of an animal that didn't receive colossum, you can see that there's already colonisation and infection with esterica coli that are damaging the intestinal brush borders that are damaging the villa, they are causing an infection, they're promoting inflammation. Whereas on the right, the calf that received colossum that was properly fed.

Vili are intact. They're perfectly fine. There's no infection, and then those IgGs you can see them there in this dark circles, .

That are showing that IgG it's being absorbed and it's also preventing infection. So It's very, very important that we can feed enough quantity and quality of collusion relatively quickly and clean for these animals. So, this is a study from Angela Blo, also from University of Michigan State, That look at feeding off coloss either 1 time or 2 times.

So they were feeding either 1 meal of Of 3 litres of coloss versus 2 mLs. Of colossum. And then they look at the incidence of disease based on just those two parameters.

And what they observe is that cows that receive two feedings of colossium, they have lower incidence or lower probability of developing diarrhoea and also lower probability of developing respiratory disorders. So, calcium is not only protecting that calf locally in the gut, it's also protecting it systemically for other disease disorders. In addition to that, another study from Angela Bela's group show using the categories that were developed by Lombard that I just explained to you that goes from excellent to bad, so excellent, good, fair, and poor, they use Calves that fit into these categories and they also look how being on one of each of these categories affected the incidence of respiratory disease and, and affected mortality of these calves.

So animals that had excellent and good passive transfer of immunity. They have much lower incidence of respiratory disease, and also they have much greater chances of surviving throughout the 1st 80 days of life. I just mentioned that.

Quickness, quickness of how quickly we deliver that colossum into the calves also affects Passive transfer of immunity. So this is a study from Mike Steel's lab from Canada, where I did my PhD in looking at feeding a colossum replacer that was, is the same colossum replacer, but the only difference is that it was first, it was fed right at birth when those animals were born or fed at 6 hours after or 12 hours after. And we measured immunoglobulin concentrations in circulation.

During the 1st 40 hours of life. And what we can see. Is that the animals that were fed at birth, they had much higher concentration of IgG or they reached much higher concentration of IgG which also stayed higher for those 48 hours compared to calves that were fed at 6 or 12 hours.

So you could be starting with a good quality colossum, but if you delay the feeding. Post 6 hours, you are reducing the ability of that calf to absorb those IGGs. So you could be starting with a good quality option, but if you feed it later, you're actually going to fall into a different category, not because of the quality of the collection, just because, but because you're feeding it late or you're like taking too long to feed the collion.

I'm not asking producers here to feed Colossum right at birth or within the first hour, but I'm trying to make a point that the fastest you can deliver that Cossum to the animal. The better chances that animal is going to have to absorb successfully those IGGs and that animal is going to be more protected during the previous period. So, this is a graph of failure of passage transfer of calves during the pre-mit period.

And this is where I remain very hopeful that this is only from 15 years ago. Close to 40% of calves in Canada in the province of Ontario had failure of passive transfer of immunity. And now the number has dropped down to close to 24%.

So definitely we're going in the right direction, but there's still a lot of work to do. We had, we get a lot of questions. From producers of what do we do if we routinely have collusion that is, is not of enough quality or if we don't get enough couption to feed and support our cats.

And something that has proved really useful is enriching colossum with colossum replacement. So this is a study from a colleague of mine that They measured Cerro IGG. Sorry, they, they used colossum that either had low quality, so had 30 grammes of IgG per litre.

Or maternal colossum that has good quality or very high quality of colossum, and then they measure serum IgG on those calves 24 hours after. But then they say Can we enrich low quality co with colossum replacer and try to achieve similar values here. So that's exactly what they did.

So they enrich colossum replacer enrich a maternal coloss of low quality with collageumum replacer and they were actually to greatly improve pass the transfer of immunity in those gaps. Then they try to do the same thing. Of going from a good quality coloum, 60 grammes of IDG per litre to high quality also further enriching that colosum, but they seem to reach a plateau where the, after you get a good quality collum close to 50 to 60 grammes and reaching that coum doesn't seem to have an added benefit.

But if you have a low quality colossum, And you don't have another source, you could be enriching that with colours and placer and then achieving similar values of passive transfer of immunity. So, in reaching low quality colossum with colossum replacer. Maybe a feasible strategy to ensure passive transfer on these scenarios where we don't get either enough couption that we all know that there's a big seasonal variation on the amount of coloss that is produced from these dams.

And so this could be a good way of tackling that. In addition to that, it's important to know and understand that colossum is not only immunoglobulins. There's a lot of bioactive factors that are present in colossum.

That play very important roles in promoting intestinal development, in promoting the type of bacteria and microorganisms that are going to colonise that cat, and also promoting overall development of that cath. So, in addition to immunoglobulins, We have actual antimicrobial compounds in there like lactoferine. We have growth factors in there.

We have different profile of fatty acids, and we also have something that is called oligosaccharides that are actual prebiotics that are synthesised just in this period by the mammary glands. And those probiotics are only used by specific group of microorganisms. So these are targeting, that, that gap, it's colonised by a specific group of microorganisms that promotes very beneficial functions for the calf.

And when we think of how we manage collusion feeding on farms, sometimes we're only feeding one feeding of coloss or at the most 2. And after that we're switching into milk or meroplazer, but in nature, that animal would have a continuous exposure to them and will be receiving this very beneficial bioptic compounds, that typically on farm and have on a commercial farm is going to be restricted from these compounds. And we can pick up beneficial differences even when we're increasing the amount of colossum that we're feeding or if we're increasing from 1 to 2 feedings of colossum in terms of increased average daily gain of those calves throughout the premiuming period.

And even something that is very, very interesting is that we can still continue to pick up differences all the way to 2 lactation of these animals. So more than 3 years after. We use this stream and that was only on the first day of life, we're still seeing effects.

From feeding, a second feeding of collusion. And also milk yields throughout 1st and 2nd lactation are actually, And increase by increasing feeding of, of, of cossum in these animals. So it is important to note in here that colossum is not only providing nutrients and protection against disease during the early period, but it's overall programming that animal to be the best version it can be.

And if you're restricting somehow colours and feeding on these animals, we are actually reducing that genetic potential of these animals. This is another scenario here where calves were fed either 1 or 2 mils of colossum and we observe the same thing in terms of average day gain. Animals that received 2 feedings actually grow more and they also produce more milk during the first lactation.

So, OK, now that we've finished talking about feeding, what are some of the things that we can do post day one of life to improve gut health and reduce incidence of disease? It's still, it's related to colossum feeding. And What we call transition milk.

So, as I was discussing with you, if that animal was in nature with its dam. Would be consuming colossum and then there's going to be a natural transition on the composition. Of the initial milk all the way until it gets to a point that .

It's, it achieves the concentration and composition of what we consider mature milk or soluble milk in the milk that, that, that, that, that we're going to sell. And there's a natural transition in nutrients, so dry matter, fat, protein, and, but also on those bioactive factors. But what happens on commercial farms, typically those cows are gonna receive either 1 or 2 feedings of mushrooms at the most, but they're not receiving this transition milk because it's difficult to manage on farm and they are switched into either whole milk, waste milk, or milk replacement.

But they are missing out on these very nutrient rich and, and valuable milk that is a transition milk that we should try to be finding ways that we can try to incorporate this into Into our nutritional strategies. So, there's actually been studies looking into that where they either extend Colum supplementation in the metro laser, so creating something that would look similar in the profile to what is considered transitional. And in this case, in this study, they extended colossom feeding for 14 days and they look at incidence of disease.

These calves, they were supplemented with Clos, they had lower diarrhoea and respiratory disease, and they actually needed less treatments with antibiotics. In addition to that, another study, a more recent study, they look at supplementation of milkplar with either 350 grammes of colossum replacer or 700 grammes of colosum replacer, and they look at incidence of disease under these scenarios, very simple study. And they saw also a reduction of pneumonia cases.

And also the duration of pneumonia was, was reduced. And also the duration of diarrhoea was reduced when those animals were fed 700 grammes of collagen replacer in the milk replacer. There's also been recent studies trying to use colossum as therapy for diarrhoea where when an animal was detected to have diarrhoea, they will receive either colossum, or feedings of colossum.

In the milk laser fed at 65 grammes per litre of milk laser and 65 grammes per litre of coloss replacer in 2.5 litres, and they would feed 4 feedings of that. So that would mean that they would be fed for 2 days.

Or they would fed, they would be fed 8 feedings of that mix of 65 grammes of replacer and 65 grammes of colossum replacer in again in 2.5 litres, but it would be fed for 8 feedings, so for 4 consecutive days. And they look at resolution to diarrhoea.

So calves that were fed for 8 consecutive feedings with this combination, they resolve diarrhoea cases much faster and actually the calves. And when enrol in that group that receive those feelings actually after recovery, they grow better, they, they grow more, they grow more. In addition to that, Feeding feeding a second meal of coloss or transition milk on the first day of life can also have an impact on passive transfer of immunity as measured here by IgG concentrations in circulation on those graphs post 12 hours of life.

And lastly, something that I want to mention or I wanna show is the important role of collusion and transition milk in promoting proper intestinal development. So, this is part of the same study that I was showing you here. Those calves were, this was a terminal study that at 24 hours of age, those animals were, were, euthanized and we look at intestinal tissues in here of cows that were fed either milk.

A second, a second feeding, so all these calves were colossum at birth, but then the second feeding was either milk, transition milk, or coloss. And you can clearly see the cows that receive a 2nd feeding of colossum, they have much better integrity of that cat and that intestinal ability is much more developed, OK? So with that, I just gave a big overview of what are some of the current management practises.

That we have on farm and how that could be positively or negatively affecting animals and then what are some of the alternatives we could be using for treatment specifically of diarrhoea on farm or prevention of diarrhoea, and most of these practises are centralised on the use of couption for various, for various roles, either preventative both at birth on the first day of life and post day one of life. And also as a way of trying to reduce the incidence of disease throughout the entire preming period. A last point I want to make is, or, and a last strategy I would like to mention is the use of probiotics.

So, There's a lot of talks and discussion and research on the role of probiotics. There's high variability on the response you get from probiotics because you have many different types of pro and prebiotics in the market. And so I just want to make this.

Overview of a publication that we did in 2020, that was a, a narrative review looking at 14 different papers that the yeast, yeast supplementation took up during the pre-ming period. The most consistent response that we observed with feeding of yeast, for example, sacroysis cerviia and sacromycericiabulardi, was on reducing incidence of disease. And then one of the most consistent effects that we observe its marginal increases on average daily gain.

So, something that I always try to emphasise when I discuss producers strategies of using probiotics is you're not going to get very significant improvements on average daily gain. As you can see here, it, it's very dependent on the context and the environment. You have some variation on the response you're gonna get.

Also, this is because they're using different strains and probiotic products. But overall, you seem to have an effect on average daily gain. But that might be driven actually by the improvements on gut health and reduction of diarrhoea on this scas.

And this is a study from Kilda Bello from, from Loloud, from a couple of years ago that they fed sacromycericia bulardi to cows and they look at the faecal scores and the incidence of diarrhoea, total diarrhoea cases, and cows that were fed the sacromycerbeia bulardi, they actually had a reduction in diarrhoea cases. And They try to go one step further and try to understand what was the the mechanism of action for this probiotic strain and in reducing incidence of disease, and they fed calves this, this probiotic product in calcium and plar. Then these caps were dissected and so it was also a terminal study.

And then they looked in their gut, the production of immunoglobulin A, which is the main immunoglobulin that is produced by immune cells in the gut. To try to reduce the abundance of pathogenic bacteria or pathogenic microbes, and they saw that the calves they were receiving sacroysis, they actually had increased secretory IGA concentration in the ilium and in the faeces. And when they look, when we look at microbial diversity, that as I mentioned at the beginning, it's very much related.

To the ability of that immune system to develop properly. We saw that calves that receive this probiotic, they actually had an increase on microbial diversity. So what we think is happening here is that this probiotic is actually Enhancing the process of microbial colonisation and accelerating the maturation process and in turn, that is promoting signals in that intestinal environment to pro to promote a much better intestinal function and immune function during that process.

OK. So, with that, I would like to thank you all, for listening to this presentation, and I hope you enjoy the, the, the slides. Thank you.