Dr. T.G. Nagaraja: The Abscess Obsession
The following is an edited transcript of Nicole Erwin's interview with Dr. T.G. Nagaraja. Click below to hear the full interview:
Nicole: I'm talking with Dr. T.G. Nagaraja, University Distinguished Professor of Microbiology in the College of Veterinary Medicine at Kansas State University. Dr. Nagaraja joins me to talk about a major issue in feedlot cattle: liver abscesses — a problem that can bear significant economic cost to the producer, packer and even the consumer. Dr. Nagaraja, thank you for joining us.
T.G.: You're welcome.
Nicole: Can you tell us a little bit about how you've come to specialize in the gut microbiology of cattle, specifically the rumen microbes? For those of us who understand that cows have a unique system for digestion but might not have the full capacity to appreciate it, what is it about rumen microbes that you've come to appreciate most?
T.G.: I've been working in the area of rumen microbiology for the past 30 to 35 years. Rumen, as you know, is the first compartment of the four-compartment stomach in cattle. Rumen has a lot of microorganisms. In fact, when we feed cattle, we are feeding the microbes, not the animal. What microbes do is break down the feed into nutrients that the animal can then use. The microbial activity in the rumen provides both energy and protein to the animal.
My research interests have been in beef cattle, particularly cattle fed a high-grain diet. This would be what we call “feedlot cattle,” meant for beef production. When we feed a high-grain diet — because grain is starch, and starch is a highly degradable or digestible carbohydrate — therefore, microbes break it down rapidly and produce a lot of acid. Because of that rapid fermentation, there are a lot of digestive problems in cattle. That has been my area of research: how to minimize those digestive problems.
Nicole: What happens when the microbial colonies get out of balance? Is there a way for producers to see physically or behaviorally that their cows aren't feeling well?
T.G.: It's difficult to see unless the production of acid exceeds the capacity for the animal to absorb and utilize nutrients — in which case, the rumen acid concentration increases to a level that reduces animal feed intake. That's when producers will notice that cattle are not doing well, because they're eating less than what they are expected to eat. That condition is called acidosis, and that's a very common problem in grain-fed cattle. That increased acid production and increased accumulation of acid in the rumen causes a lot of digestive problems.
Nicole: With feedlot cattle, are producers able to keep an eye on them as frequently as they would like? I mean, could this kind of go undetected?
T.G.: In a feedlot, where you have hundreds of animals in a pen, it's very difficult to detect acidosis unless the animal is extremely sick, in which case you will see the animal standing by itself, away from the feed bunk. Usually, the pen riders who keep an eye on the cattle can spot those animals and maybe pull those animals out of the pen to treat them.
Nicole: Can we determine rumen community composition by how we feed and raise the calf or heifer?
T.G.: It's a lot more complicated to understand all the microbial changes that take place with different feedstuffs. One unique aspect of microbes in the rumen, in microbiology, are called anaerobic organisms, which means they live and grow without using oxygen. Therefore, if you want to study them, you have to have special techniques to grow them outside the rumen in the lab. These are what we call “anaerobic techniques.” Rumen is a very complex ecosystem — there are bacteria, there are protozoa, there are fungi — and it's not easy to understand all the changes that take place in the rumen when you, for example, change the diet of an animal.
Nicole: The new veterinary feed directive has sent a message that traditional antibiotics approved for the prevention of liver abscesses should be a last resort instead of a preventive method. Because of that, we're hearing more about the use of ionophores, for instance. How are these safer than tylosin or other antibiotics used to prevent abscess?
T.G.: Tylosin is the antibiotic of choice to prevent liver abscess. That seems to be the best one. Whenever we feed antibiotics to animals, there is always a chance that we may be creating some resistance in bacteria — which may end up in humans and could be a public health concern. Tylosin is not used in human medicine. This is a drug used only in animals, but it belongs to a class of antibiotic called macrolide. The same class includes another antibiotic that is commonly used in humans, and that is erythromycin. In fact, tylosin and erythromycin are very similar. So, if bacteria becomes resistant to tylosin, it could also be resistant to erythromycin. That is the reason why we are concerned about feeding tylosin.
With the new veterinary feed directive, the intent there is that we cannot use antibiotics for growth promotion. Tylosin is used to prevent infection in cattle. That's why the U.S. Food and Drug Administration (FDA) has allowed tylosin to be used, as long as it is under veterinary supervision, until the industry comes up with a different method to control liver abscesses.
Nicole: Other methods are also being explored, like the use of certain essential oils, yeast fermentation and product consumption. What are your thoughts on these as a method of prevention in treatment?
T.G.: I will say we should be able to develop other methods that do not involve use of antibiotics. One of them is probiotics. Probiotics are beneficial bacteria, but some of them do produce substances that could kill other bacteria. For example, we know that probiotics can reduce Salmonella in chickens, swine and cattle, or reduce Shiga toxin-producing E. coli, which is a major food-borne pathogen. Similarly, there could be a probiotic that could be used to kill the bacterium that causes liver abscess, which is called Fusobacterium necrophorum. As of now, we don't have any probiotic identifier, but there are people, including in my lab, looking at those probiotics.
The one that has shown some promise is essential oil. These are products of plants. That means they are natural products. But many of the essential oils behave almost like antibiotics in the sense that they do kill bacteria. We have looked at a few essential oils and have shown in a lab, in a test tube, that some of the essential oils can kill bacteria that cause liver abscess. The question is if we can feed those to cattle and, thereby, reduce liver abscess prevalence. That work has not been done yet.
Nicole: What kind of restrictions might there be in making those more available? Do you have to go through the FDA?
T.G.: Essentials oil are considered what we call “generally recognized as safe products,” or GRAS status. This means they would not require FDA approval, because these are natural products, naturally safe. As long as the industry can show that the product is effective in reducing liver abscess, it should be commercialized. It would be a lot easier to commercialize essential oils than antibiotics, for example.
Nicole: How would you provide the essential oils to the cattle? Would it be in a capsule? Would it be on the feed?
T.G.: This would probably be mixed with the feed. It could either be a liquid product or it could be dry powder, because some of the essential oils are available as powder. It could be mixed with the feed, so it would be easy to administer to cattle.
Nicole: Certain breeds of cattle seem to be affected by liver abscesses more than others. For example, I've read that Holsteins have the greatest incident rate, followed by dairy cows and then fed-beef steers. Why is that?
T.G.: I think the reason why Holsteins have a higher prevalence of liver abscesses is simply because they are on a high-grain diet for extended periods of time. Typically, Holsteins used for beef production are Holstein calves. What producers do is start the calves on a grain diet right after they are weaned off of milk. Typically, a Holstein steer, before they go to slaughter, would have been on a grain diet for 300 to 350 days, as opposed to beef cattle meant for beef production. Those are typically on a grain-fed diet for 3 to 5 months, or 120 to 150 days. I think the duration of grain-feeding, we believe, is the major reason why Holsteins have higher liver abscess.
Nicole: I think I saw a number around $64 million annually for the beef industry in the United States for losses associated with liver abscesses. How does abscess extensively affect an entire industry?
T.G.: If you look at the average prevalence of liver abscess in feedlot cattle in this country, it would be anywhere from 10 percent to 20 or 25 percent, even with feeding tylosin. Tylosin is effective in reducing liver abscess but does not eliminate the problem. Liver abscesses could cost the producers as well as the packers. It affects producers because cattle with liver abscesses — particularly those that have what we call in the industry “A+ liver abscess,” which would be a liver with a large abscess or multiple small abscesses — when they have those A+ liver abscesses, the animals don't eat as much, they don't gain as much and they become less efficient in converting feed into gain. That costs money for the producer. Once the cattle go to the slaughterhouse, obviously even a minor liver abscess could be condemned. So that's a loss of liver for the packer.
Plus, many times when we see livers with abscesses, they adhere to the adjacent organs, like diaphragm and lungs. So that leads to a lot of trimming of the meat, so there is a reduction in carcass yield because of liver abscess, and that costs money for the packer. The cost of the retail price I was told is about $5-6 per liver, so that's the minimum loss. In terms of carcass yield reduction, that could be anywhere from $25 to $75, depending on the extent of trim they have to make.
Nicole: You mentioned that there is still a lot to learn about the essential oils and probiotics. How far do you think we are from getting probiotic strains to persist in the rumen and in the industry?
T.G.: We still have not identified the probiotic product that does affect the bacterium that causes liver abscess. We know some essential oils do. The question is whether the effect it shows in the lab — does that translate in the field? That's where we need to do more studies. There is always the question of whether the bacteria may get adapted to essential oils. So, if you feed it for three to five months, they may lose the efficacy. Those are the types of studies we need to do.
If I could mention, one other way we could control liver abscess would be to have a vaccine against the bacteria. Just like there are a number of vaccines to treat bacterial diseases, liver abscess is a bacterial infection, and we know which bacterium causes liver abscess. One of the approaches we have taken in my lab is: could we develop a vaccine? We are targeting two different structures or products for the bacteria. One is a protein that's on the surface of the bacteria, and we have evidence to believe that the protein is the one that attaches the bacteria to the cells in the animal. That attachment is a prerequisite for infection. If it prevents that attachment, we may be able to prevent the infection. That's one approach.
The other approach that we have been working on is when the bacterium goes to the liver — the liver is a very well-defended organ — there are a lot of mechanisms to combat foreign bacteria. So, when Fusobacterium necrophorum — the one that causes liver abscess — goes to the liver, the reason why it can survive is because it produces a toxin that kills white blood cells. Normally, white blood cells would be the first line of defense in the animal. When bacteria go into the organ, white blood cells engulf the bacteria and destroy them. This organism (Fusobacterium necrophorum) produces a toxin that kills those white blood cells.
What we're trying to do is have a vaccine containing the leukotoxin as well as a protein that mediates attachment, to see if the animal has antibodies against those. Then, a vaccinated animal may be able to prevent attachment, then prevent the survival of the bacteria in the liver. We think this may be the way to prevent the infection.
Nicole: Well, which one do you think would come first: the vaccination as a solution, or probiotics? Where are you furthest in your research?
T.G.: I think, with vaccines, we are working on it. Again, a vaccine has to go through a lot of regulatory approval. That may be at least another 2 to 3 years in the making, whereas probiotics or essential oils would be a lot faster to bring to the market. In fact, there could be probiotics already being used that could have an effect, but nobody has tested those.
Nicole: Dr. Nagaraja is a distinguished professor of microbiology in the College of Veterinary Medicine at Kansas State University. Thanks for joining us.
T.G.: Thank you.
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