Gut Health From Every Angle: 360° Concept for Gut Health.

We all know gut health is essential for livestock, but it's more than just avoiding problems. A healthy gut is the cornerstone for optimal performance, impacting both animal well-being and your bottom line.

Feed additives like probiotics, prebiotics, and toxin binders, can be powerful allies in promoting gut health and animal performance. They support beneficial gut bacteria and create a thriving environment. They can also help irreversibly bind harmful toxins and pathogenic microbes, providing protection.

In this way, additives can help reduce the impact of the “bad guys” that can disrupt gut health and performance and support the “good guys” that aid in digestion and immune function. Indeed, a holistic approach will be the most promising one to preserve the complex nature of gut health.

Microbial probiotics.

Probiotics are live microorganisms that provide health benefits to the host when administered in appropriate amounts. There are three main categories of probiotics in animal nutrition: spore-forming bacteria, lactic acid bacteria, and live yeasts. Each has their strengths and weaknesses.

Spore forming bacteria are heat stable and have the advantage in pelleted feeds. These bacteria are used primarily in monogastric animals. They produce digestive enzymes to improve feed conversion and are especially known to inhibit gram-positive pathogens.

Lactic acid bacteria are often used in young animals because they become active in the gut more quickly than other probiotics. These bacteria are prolific producers of lactic acid and are known to reduce gram-negative pathogens.

Live yeast fermentation activity promotes positive ruminal and intestinal microbiota, leading to pH stabilization in the rumen and intestine and thus to better digestive capacities. This results in improved health and performance.

There is one species of bacteria that combines the best of both—Bacillus coagulans. This is currently the only known probiotic that is both heat stable and produces large amounts of lactic acid. This means that this probiotic survives the pelleting process, and provides gram-positive and gram-negative bacteria inhibition, digestive enzyme production, and overall improvement of the intestinal environment (Figure 1).

Figure 1: The different main advantages of Bacillus probiotics, lactic acid producing probiotics, and B. coagulans,

Biochem's unique strain of this exceptional probiotic is TechnoSpore® based on B. coagulans DSM32016 and has been EU registered since the end of 2020. It's also the first B. coagulans registered in the EU for animal nutrition and remains the only one available for this use.

TechnoSpore® supports the microbial balance and reduces harmful bacteria. As such, it is effective against intestinal disorders and digestive problems. It improves protein digestion and thus supports muscle health and growth. It benefits the host's immune system and as such can positively affect respiratory health.

TechnoSpore® B. coagulans DSM32016 supports intestinal health directly and indirectly by using several modes of action including competitive exclusion, organic acid production to improve the gut environment, and pathogen inhibition.

TechnoSpore® has been shown, with in vivo testing, to:

• Reduce mortality in challenged and unchallenged animals

• Reduce intestinal and cecal C. perfringens counts

• Reduce pathogen-induced intestinal lesions

• Reduce pathogen-induced intestinal epithelial damage

• Improve villus height and villus/crypt ratio for increased nutrient absorption area

• Stabilize feed conversion and improve FCR in challenged and unchallenged animals

• Improve body weight and control performance declines in challenged and unchallenged animals

Yeast-Derived Functional Prebiotics.

Prebiotics are non-digestible carbohydrates in food that help the growth and activity of beneficial intestinal bacteria. Although prebiotics come from a variety of foodstuffs, one source of highly functional prebiotics are lysed yeasts, which can be the whole yeast or just part of it, like yeast cell walls. Yeast-derived prebiotics offer more than just the classic prebiotic effects. Further, they offer pathogen binding and immune stimulating effects and, for special yeasts, increased palatability.

A commonly used yeast for prebiotic purposes is from the species Saccharomyces cerevisiae. Either whole yeasts or parts of yeasts, such as yeast cell walls, are often used as functional feed materials. The main functional ingredients from the yeast cell wall are mannan-oligosaccharides (MOS) and β-1,3/1,6 glucans. The composition of yeast cell wall products is predicated by the processing and the origin of the yeast, among other factors.

Mannan-oligosaccharides also have known effects on intestinal structure and function such as significantly increased and strengthened intestinal epithelial surface area (increased villus length), resulting in improved bioavailability of nutrients in the small intestine and stronger gut barrier for protection from pathogens.

TechnoMos® positively influences gut health by supporting gut eubiosis. The high MOS level in TechnoMos® helps to efficiently bind gram-negative pathogens, making them harmless. The β-1,3/1,6 glucans in TechnoMos® have been shown to increase the functionality of the immune system.

In addition to yeast cell walls, yeast extracts provide additional benefits. One such product, including both yeast extracts and cell walls, is TechnoYeast, derived from the primary cultivated yeast Kluyveromyces fragilis. This unique yeast strain has a specific milky-umami flavor and further delivers many functional ingredients that support feed intake, immune status, and finally gut health.

TechnoYeast provides nucleic acids that are a source of nucleotides, which are important for growth, immune support, and intestinal health. These nucleotides also function to increase palatability of the product. Next to that, TechnoYeast is a source of highly bioavailable proteins, such as essential amino acids like lysine, threonine and valine, as well as palatable amino acids, like glutamic acid.

Feed intake is a key factor in the successful rearing of young animals. In fact, there is a significant positive correlation between intestinal development (villus height) and dry matter intake in weaned piglets (Figure 2). The higher the feed intake, the better the intestinal development, resulting in better digestion and nutrient absorption.

Figure 2: Positive correlation of feed intake and gut physiology (villus height) in weaned piglets.

Field trials with TechnoYeast have demonstrated its effectiveness in promoting gut health and improved performance. TechnoYeast significantly increases feed attractivity and reduces the incidence of diarrhea, shown by improved fecal scores. Morphologically, TechnoYeast increases villus height and improves the villus to crypt ratio. This results in improved feed conversion ratio and body weight gains. In addition, TechnoYeast stimulates the immune system, including increasing the secretory IgA, which is the first line of defense against toxins and pathogens in the gut.

There are numerous beneficial effects of TechnoYeast and their prebiotics including:

• improved feed intake

• improved immune defense

• reduction of gram-negative pathogens

• strengthening of the gut epithelium and eubiosis

• improved feed conversion ratio

• improved weight gains

• enhanced animal well-being

Toxin Management.

While probiotics and prebiotics are often the first products that come to mind when considering feed additives to improve gut health, they are not the only ones. Another issue in the quest for gut health is toxin management. The categories of toxins relevant to the gut health of our animals are mycotoxins, the secondary metabolites of molds, and two groups of bacterial toxins—endotoxins and exotoxins.

Mycotoxins can affect gut health at the cellular level. The three leading cytotoxic effects of mycotoxins are the inhibition of protein synthesis, altered gene expression, and membrane damage. All mycotoxins have lipid peroxidative effects, causing increased oxidative stress at the cellular level.

Mycotoxins inhibit protein biosynthesis, resulting in a deficiency of essential proteins. These proteins include both structural proteins and functional proteins such as enzymes. In addition, mycotoxins can alter gene expression resulting in decreased cell performance.

Although cellular damage is not readily visible, the effects can be seen in the form of disease and reduced organ performance as cellular damage accumulates. Tissues with high protein turnover and rapid growth, such as the immune system, are particularly sensitive to the effects of mycotoxins. This may lead, for example, to an increased susceptibility to facultative pathogens living in the gastrointestinal tract (Figure 3).

Figure 3: The interactions of mycotoxins and pathogens in the intestine. DON has been shown to enhance the growth and toxin production of Clostridium perfringens and T-2 toxin has been shown to increase the colonization of Salmonella typhimurium in chickens. There was increased translocation of Salmonella typhimurium in pigs exposed to DON. This means that since S. typhimurium is always present in the gastrointestinal tract of the pig, DON promoted the breaching of the gastrointestinal barrier to cause systemic signs. In calves, exposure to aflatoxins resulted in increased toxin and pore-forming activity of toxicogenic E. coli. Effects of Mycotoxins on Mucosal Microbial Infection and Related Pathogenesis; Seong-Hwan Park, Dongwook Kim, Juil Kim, and Yuseok Moon.

Another tissue greatly affected by the effects of mycotoxins is the intestinal epithelium. Only one cell layer thick, this tissue is responsible for the barrier function between the outside world (intestinal lumen) and the inside world of the body. The intestinal epithelium is one of the fastest self-renewing tissues, renewing itself every few days to a week.

This makes it very sensitive to mycotoxin exposure. Even at low mycotoxin concentrations, functional disorders can be seen as reduced feed efficiency. Other epithelial structures impacted by mycotoxin exposure are an essential part of the intestinal barrier function. These include goblet cells and tight junctions (Figure 4). The loss of barrier function leads to increased translocation of pathogens and other toxic substances that are always present in the gut lumen, such as bacterial endotoxins.

Figure 4: The effects of mycotoxins on the gut epithelium. As the gut epithelium is responsible for efficient nutrient absorption, this intestinal cell disorder often will lead to reduced feed efficiency and decreased performance. Goblet cells are important members of the intestinal epithelium. They are responsible for the production of mucus, which is essential for a functioning intestinal barrier. Exposure to mycotoxins damages these cells, leading to a reduction in mucus and impaired barrier function. Another important player in the intestinal barrier function is the tight junction. Tight junctions are protein complexes that exist between enterocytes and allow precise control of which substances can pass through and which cannot. Mycotoxin contamination can result in reduced formation of tight junction , leading to increased intestinal permeability. This leads to increased translocation of not only pathogens, but also other toxic substances that are always present in the gut lumen, such as endotoxins.

Bacterial endotoxins, as the name implies, are toxins bound to bacteria, specifically gram-negative bacteria. In fact, 70 to 80% of the outer cell membrane of gram-negative bacteria is made up of these endotoxins. These endotoxins are also called lipopolysaccharides (LPS) because they consist of a lipid portion and several polysaccharide chains.

LPS are simply building blocks of the cell wall of gram-negative bacteria, contributing greatly to their structural integrity; they are present in every microbiome. Lipopolysaccharides are released when the cell membrane is ruptured, such as during cell death or during the proliferation of gram-negative bacteria. They exert their effects in their free form.

There are several other factors that determine how damaging LPS can be.

1. Location: Do they remain in the intestinal lumen, or can they cross the gastrointestinal barrier to enter the organism?

2. Number: The level of exposure to LPS.

3. Species: Some species, such as poultry, are less sensitive to LPS than others, such as ruminants and pigs.

When the intestinal epithelium is healthy and has good integrity, endotoxin uptake is controlled. resulting in a limited amount of endotoxin in the organism. These endotoxins are transported to the liver where they are presented to the immune system. In this way, the immune system is regularly trained for the markers of gram-negative bacterial proliferation.

However, when gut integrity is compromised, as in the case of mycotoxin exposure or heat stress, this controlled uptake of endotoxin becomes uncontrolled. As a result, the neutralizing capacity of the liver is overwhelmed and the endotoxin spreads systemically. Endotoxins block certain receptors, leading to an inflammatory response—the more endotoxins the more severe the response.

One such inflammatory response is Porcine ear necrosis. This disease occurs mainly in weaning piglets. A 50-day trial was performed with 408 healthy weaned piglets to determine the effects of supplementing a toxin binder on endotoxin associated disorders. Piglets (2 groups) were fed either a basal diet or the basal diet with a toxin binder (B.I.O.Tox® Activ8), which was selected because it binds all relevant mycotoxins. Groups were assessed for growth performance as well as the prevalence of endotoxin associated disorders such as ear necrosis and the feed were tested for the presence of mycotoxins.

The amount of ear necrosis was determined by visual assessment and assigning a grade depending on the amount of necrosis present pen-wise using the following scale:

• Grade 0: No piglets in the pen are affected.

• Grade 1: Less than 30 % of the piglets in the pen are affected.

• Grade 2: More than 30 % of the piglets in the pen are affected.

• Grade 3: All the piglets in the pen are affected.

Piglets supplemented with B.I.O.Tox® Activ8 had reduced incidence of ear necrosis compared to the control group (Figure 5). Moreover, when compared to the control group, severe cases were significantly reduced in the toxin binder group. Analysis of the diet demonstrated that the only mycotoxin present was DON at a level of 60 to 100 ppb. Adding B.I.O.Tox® Activ8 to the feed also resulted in reduced losses, a numerically improved feed conversion ratio, as well as better uniformity between the pens (Figure 6). These results imply improved gastrointestinal integrity with the addition of a toxin binder.

Figure 5: Prevalence of ear tip necrosis in piglets supplemented with B.I.O.Tox® Activ8 compared to the control group. The number of overall incidence of ear necrosis was reduced in the supplemented animals with the number of severe cases significantly reduced.

Figure 6: Piglets fed B.I.O.Tox® Activ8 resulted in reduced total losses (A), better pen uniformity (B), and a numerically improved feed conversion ratio (C).

The visible effects of endotoxins are only the tip of the iceberg—so much more damage is occurring beneath the surface. Good endotoxin management aims to avoid as many factors that compromise integrity as possible—such as avoiding specific pathogens, removing harmful mycotoxins, and reducing heat stress. Endotoxin-related disorders can be reduced with the smart selection of feed additives embedded in a holistic feed and management concept.

Bacterial Exotoxins

Whereas endotoxins are structural parts of gram-negative bacteria, exotoxins are direct weapons. These are proteins excreted by certain bacterial strains with possible necrotic or hemolytic effects.

The most relevant are the exotoxins produced by Clostridium and those produced by Salmonella spp. or E. coli spp. These bacteria are present in all three livestock animal groups as a normal part of the gut microbial community. So when will the presence of these potential pathogens become a problem?

The development of necrotic enteritis is a good illustration of how these exotoxin-associated diseases develop and how they can be prevented. C. perfringens produces toxins when a certain population density is reached. This critical mass can be reached due to dysbiosis and reduced immune status, but also due to physical changes in the gut, such as mycotoxin-induced leaky gut or reduced intestinal resilience (Figure 7).

Figure 7: Coccidiosis can cause immune suppression, allowing C. perfringens to proliferate and begin producing exotoxins and necrotic enteritis. Since mycotoxins reduce gut integrity, they are direct promoters of this disease.

Mycotoxins disrupt gut integrity and may increase the virulence of certain pathogens, paving the way for increased endotoxin stress and indirectly promoting exotoxin formation. They can be neutralized by specific solutions such as highly effective surface activated binding agents. Efficient mycotoxin management is the basis for holistic toxin management. Neither endotoxins nor exotoxins can be controlled by a one-size-fits-all product! For the most promising outcome, a smart approach to feed additives is required, in addition to appropriate feed formulation and management.

360-Degree Gut Health Concept

Several factors can disrupt gut health, including harmful microbes, toxins, and even some medications. To address these challenges, we need a holistic approach. This includes:

• Smart medical interventions: Balanced use of antibiotics and strategic vaccination programs can help maintain a healthy gut.

• Effective management practices: Proper hygiene and housing conditions play a critical role.

• Optimal feed formulation: Proper nutrition provides essential nutrients and supports a healthy gut microbiome.

Feed additives can make a significant contribution to a healthy gut. However, there is no single solution to all problems. Only a holistic, 360-degree approach from all angles will effectively lead to robust gut health and improved overall animal performance.