Feed additives

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Don’t kill, but tame the bacteria

Producing broiler meat with the label ‘no antibiotics ever’ is becoming a common thing in the US. In the meantime, the poultry sector fears that this leads to a less efficient system, in which it is harder to control major poultry diseases. Luckily, a new set of savvy feed additives that keep bad bacteria under control is on its way.

Poultry production under the philosophy ‘no antibiotics ever’ (NAE), is spreading like a wild fire in the US and also in some other parts of the world. Although this sounds like a good development, and it is, it also comes with challenges, both from a nutritional standpoint as well as keeping the margins and being able to sell the products. At a recent first-annual summer international poultry symposium, organised by Amlan International, the challenges and solutions for poultry producers to produce under antibiotic free systems were discussed in further detail.

Moving to no antibiotics ever not only requires a shift in nutrition, it also requires a different way of thinking, management and health management of the flocks. Photo: Mark Pasveer
Moving to no antibiotics ever not only requires a shift in nutrition, it also requires a different way of thinking, management and health management of the flocks. Photo: Mark Pasveer

NAE is not always sold as NAE

Steve Kernen from Amick Farms (OSI Group) said we have to face the facts: “Poultry giants like Tyson Foods and Perdue Foods have embraced NAE and all together, around 53% of US chickens are raised as NAE. But this development also comes with challenges, considering that in 2018, around 25% of these chickens are actually sold and labelled as NAE in the US supermarkets. That is even less than the percentage sold in 2016 (33%). That leaves the poultry producers with increased production costs, that they often don’t see reflected in the incomes and premiums paid”. According to Mr Kernen, consumers want NAE chicken to be priced the same as conventional products, but this is not possible. At the same time, the retail market is moving faster than just antibiotic free. In the US, Global Animal Partnership (GAP) by 2024, organic and GMO free are believed to be the next big thing that consumers want. Some of the US poultry experts are afraid that this slows down the mission to feed the growing world population in the future. Also Dr Phillip Smith, poultry nutritionist at Tyson Foods and speaker at the event, addressed that NAE is a complex issue. “Tyson Foods has chosen to be completely NAE and we see that the rest of the world is heading to NAE production at a fast pace. The problem is that we have to give in on efficiency (average daily gain and feed conversion ratio), increase production costs by about 5-15% and controlling coccidiosis and clostridia diseases will be harder. This requires more emphasises on nutrition and health management, which was further explained by a number of expert speakers at the event.

Solving the nutritional challenges

Going for NAE is often done in combination with an all vegetarian diet for the chickens, something that they call NAE+ at Tyson Foods (no ionophores, AGPs and an all vegetarian diet). Although antibiotic resistance is a natural thing happening in nature, the livestock sector has been pushed to move away from preventive use of antibiotics. “So this is what we have to do”, explained Dr Smith. “This means we have to do things better in the hatcheries and in the feed, especially when we can’t use animal proteins, by-products and tools like ionophores anymore, like we do in the NAE+ system. But from a nutritional perspective and environmental standpoint it has many benefits. By-products such as feather meal provide the birds with a good set of amino acids. When we feed a complete vegetarian diet, a set of things have to be kept in mind and this already starts at the feed mills when the pellets are produced”, said Dr Smith. He advocates to use larger particle sizes (for example grain: 800 – 1,000 micron size grind) and to avoid if possible powdery or fine textured feeds. Courser feed is better for the gut, the birds like it better and courser feed has a better enzyme release. In addition, it is important to formulate on a digestible amino acid basis and some have recommended reducing crude protein levels to reduce overload of Clostridium in the lower gut, with an increased change of developing necrotic enteritis. It is all about being more precise”, he said. Dr Smith also addressed that utilising exogenous enzymes is important, minimise drastic feed changes (from corn to wheat for example) and to lower sodium specification (to keep moisture in the manure down) if utilising high phytase levels.

The clay mineral calcium bentonite is able to bind a range of different toxins, varying in molecular weight. Amlan is using technology to manipulate the clay mineral to be used for different applications. Photo: Emmy Koeleman
The clay mineral calcium bentonite is able to bind a range of different toxins, varying in molecular weight. Amlan is using technology to manipulate the clay mineral to be used for different applications. Photo: Emmy Koeleman

Understanding what is happening in the gut

Moving to NAE not only requires a shift in nutrition, it also requires a different way of thinking, management and health management of the flocks. To effectively control poultry diseases and to improve efficiency of the feed and hence the whole production system, an optimum working gut microbiome is key (also often referred to as ‘gut health’). Think about it: the enteric microbiome contains ten times more cells and 75 times more genes than the host. A healthy gut is able to take up the nutrients and contains a healthy balance and a mix of bacteria. If the microbiome is out of balance, the animal is more prone to diseases and also the changes of developing the so-called ‘leaky gut syndrome’ increases, causing all kinds of inflammation and enteric diseases. This in turn leads to losses in growth and performance of the birds. Enteric diseases in poultry are commonly caused by bacterial infections from Clostridium perfringens, Salmonella spp and E. coli. Dr John Maurer from the University of Georgia in the US updated the audience on the future of Salmonella control and delved deeper into the concept of competitive exclusion. Today, birds are often vaccinated against Salmonella. But he questioned if this is an effective way to keep the bacteria under control. “Vaccination does have some challenges, including regulatory hurdles and there are too many serotypes to vaccinate against. In addition, vaccination doesn’t guarantee that the farm is Salmonella-free. So which other measures can be implemented to reduce Salmonella prevalence as much as we can in a time where Salmonella becomes more resistant to a range of antibiotics and forms a great threat to humans?” Dr Maurer explained that ‘competitive exclusion’ has potential. Trials in which caecal microbiota was fed to young chicks followed by a challenge with Salmonella showed positive results. ‘Feeding’ the mature microbiome to the young birds was able to block Salmonella colonisation. This in turn has paved the way for a number of competitive exclusion products that have been developed since. “At our University we did some studies trying to figure out was what going on in the gut. We found out that diversity is key. When a more diverse number of different bacterial species is present in the gut, less Salmonella is present. A research group in Australia had the same experience with Clostridium perfringens. “We then delved into the development of tools to screen the bacteria and how they behave, that helped us develop next generation exclusion products”, Dr Maurer said. He learned that Salmonella is a scavenger and is depending on the food scraps that are available in the intestine. By adding bacteria that are competing for the same nutrients, having the same metabolic pathways, you are can fight the Salmonella, and thus competitive exclude Salmonella. “Other options for Salmonella control include the use of feed additives such as organic acids, probiotics and prebiotics and products that physically bind or block Salmonella colonisation of the small intestine or caecum”, Dr Maurer explained. He sees potential in using such products in combination with Salmonella vaccination to create a synergy effect but he also addressed that more research is needed in ‘competitive exclusion’ and that products need to translate into significant reduction on meat and egg contamination and have a reasonable price.

In October, 2017, Amlan opened the Richard M. Jaffee Laboratory for Applied Microbiology located at the company’s Innovation Center in Vernon Hills, Illinois. Photo: Emmy Koeleman
In October, 2017, Amlan opened the Richard M. Jaffee Laboratory for Applied Microbiology located at the company’s Innovation Center in Vernon Hills, Illinois. Photo: Emmy Koeleman

Binding the bacteria and their biotoxins

Products that physically bind or block bacteria colonisation, as mentioned by Dr Maurer as a possible way to reduce prevalence and contamination of a certain pathogen, are on the market and have been tested for their efficacy. During a presentation made by Amlan International experiences with a formulated product, Varium™, hereafter called product A) was further explained. Product A, containing a blend of functional additives, has the innate ability to agglutinate bacteria. Product A is includes a specially selected yeast strain and an activated mineral and was able to effectively bind the gram-negative bacteria E. coli and Salmonella enterica, which helps reduce or prevent bacterial adherence to the intestinal barrier. The same product is also able to stimulate innate and adaptive immunity and neutralise the toxins that Clostridium perfringens (causing necrotic enteritis) and E. coli release (also known as biotoxins). Some of the biotoxins that Clostridium perfringens produce are alphatoxin (α toxin) and NetB toxin. E. coli bacteria produce the biotoxin Shiga toxin. These biotoxins are far more toxic than mycotoxins and can result in significantly depressed weight gain with associated increases in flock mortality: a heavy economic burden on producers. A trial, done by scientists from the Agricultural Research Service (part of USDA) in the US tested the ability of product A to bind Clostridium perfringens and E. coli biotoxins in vitro by using ELISA tests. It was shown that binding of clostridial α-toxin and NetB toxin increases significantly as the ratio of product A to toxin increased from 25:1 to 100:1. A dose-response effect was also seen on the binding of E. coli biotoxins. The product was also tested against an antibiotic on its effect on broiler performance. It was shown that the mortality-adjusted feed conversion ratio improved for the day 0-14 period and overall when the antibiotic (bacitracin methylene disalicyclate) or product A were added to the control diets (although not significant). A trial in Peru showed decreased mortality and improved feed conversion in broilers when fed product A. The improved performance associated with this showed a significant return on investment. Touched shortly on during the seminar was also another binding product called Calibrin-Z. This is a multi-species product, designed to provide broad-spectrum control of fungal and bacterial toxins including: Clostridium perfringens, E. coli, Salmonella, Vibrio parahaemolyticus, mycotoxins and gossypol (found in cotton). This product is a thermally activated mineral that chemically absorbs the toxins, reducing their effects on the intestinal barrier.

Amlan International: From source to market

Amlan International is a subsidiary of Oil-Dri Corporation, a company that is adding value to sorbent minerals. Oil-Dri owns several reserves and manufacturing facilities throughout North America where it delves three unique mineral types to be used for different agricultural sectors, such oil industry (purification), crops and horticulture (carriers) and animal health (feed additives for intestinal health) as well as consumer applications. Around 20 years ago, the company started to sell their unique material as pellet binder and material flow aid for the animal feed industry. In 2007, Oil-Dri founded Amlan International, focusing on health promoting feed additives . The product portfolio includes additives that target fungal toxins (mycotoxins) and bacterial toxins (produced by bacteria). In October, 2017, Amlan opened the Richard M. Jaffee Laboratory for Applied Microbiology located at the company’s Innovation Center in Vernon Hills, Illinois. This lab is fully focused on developing and improving the animal health portfolio for poultry, swine, dairy and aquaculture. In 2018, the company will launch three new, natural alternative products for livestock disease management; an antimicrobial, an anticoccidial and a performance enhancer for layers.

Disrupting the communication between bacteria

Next to binding, you can also interfere with the communication between the pathogenic bacteria to make them less virulent, a novel technology that is known in human medicine, but not in livestock. What does it entail? Most bacteria send out signalling molecules to bacteria from the same strain. This is done to be able to work together and to become more fierce when needed. “Bacteria are complex creatures and have social behaviour among each other. They use communication signals and these type of soluble small molecules are specific, meaning that they often can only communicate with the same strains. They are constantly making these signalling molecules”, explained Dr Marvin Whiteley, Professor of Biological Sciences, Georgia Institute of Technology in the US. The concept of interfering with bacterial cell-to-cell communication with small signal molecules is also known as  quorum sensing and is already a known concept in human medicine. Distorting this communication system keeps the bacteria tame and less pathogenic. This is also favourable instead of killing the bacteria (what antibiotics do). The mode of action of antibiotics (antimicrobials) is killing the bacteria and the risk of this is that some may survive, become stronger and less susceptible. In turn, the resistant genes can be passed on when these bacteria repopulate, hence the increase risk on antimicrobial resistant bacteria. “It is also not a bad thing to have pathogenic bacteria colonise the gut, as these bacteria are pretty much anywhere around us. A healthy animal can deal with it and by keeping the bacteria tamed by preventing that they signal with other, there is no need to kill them”, said Dr Whiteley. In an era where we desperately are looking for a silver bullet for healthy animal production without the need for antimicrobial growth promoters or additional antibiotics, the potential of quorum sensing for the livestock sector is huge. By using this concept in animal health and nutrition, nutritionists and farmers have a new tool added to increase health, performance and farm margins under farming systems that are free from antibiotics. Amlan International is using this quorum sensing technology in their products. It opens up a new way of looking at health management in farm animals to withstand the current and future challenges such as antibiotic free production systems.

4 comments

  • Sean Griffin

    Thank you for writing a most interesting article. The bacterial communication system defined as quorum sensing is a complicated new frontier in bacteria research. In your article you mention "The concept of interfering with bacterial cell-to-cell communication... also known as anti-virulence therapy or quorum sensing, used in human medicine ...)."

    My understanding is that anti-virulence therapy is a way of disrupting the innate quorum sensing communication system of bacteria. Anti-virulence therapy therefore is not the same as quorum sensing. See reference understanding below.

    Quorum sensing (QS) is a bacterial cell–cell communication process that involves the production, detection, and response to extracellular signaling molecules called autoinducers (AIs). AIs accumulate in the environment as the bacterial population density increases, and bacteria monitor this information to track changes in their cell numbers and collectively alter gene expression. QS controls genes that direct activities that are beneficial when performed by groups of bacteria acting in synchrony. Processes controlled by QS include bioluminescence, sporulation, competence, antibiotic production, biofilm formation, and virulence factor secretion (reviewed in Novick and Geisinger 2008; Ng and Bassler 2009; Williams and Camara 2009). The anti-virulence topic you introduce in your article is one that describes a promising manipulation of the QS system with the goal of benefiting the host animal.

  • Emmy Koeleman

    Dear Sean, thank you for the comment. You are right. I have amended the sentence. Best regards Emmy

  • DONGPING WANG

    Very good article.
    "The mode of action of antibiotics (antimicrobials) is killing the bacteria and the risk of this is that some may survive, become stronger and less susceptible. In turn, the susceptible genes can be passed on when these bacteria repopulate, hence the increase risk on antimicrobial resistant bacteria."
    "susceptible genes"means genes that make the bacteria more susceptible to antibiotics. I guess you are saying "resistant genes"

  • Emmy Koeleman

    thank you Dongping. you are right. I mean resistant genes.

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