Locking in Gut Integrity: How butyrate secures optimal health

For many challenges in the animal industry, the underlying cause is an impaired gut integrity. Pigs and poultry species benefit from rapid intestinal development and an established gut integrity as a basis for overall gut health and zootechnical performance. Since butyric acid has numerous benefits for the gut barrier functioning, butyrate-based additives are key ingredients in livestock diets for a healthy start and prolonged productivity.

Arno Duchateau
Global Product Manager
Impextraco

In animal nutrition a lot of attention is given to strategies that optimize gut health by focusing on establishing a stable and diverse gut microbiome. However, in many practical situations where diet changes, antibiotic reduction and environmental stressors influence performance, maintaining gut integrity – or the physiological functionality of the intestinal barrier – may have a more immediate and significant impact on animal performance and welfare.

WHY GUT INTEGRITY SHOULD BE A PRIORITY
Evidently, our industry has a central focus on gut health as dysfunctional gut is directly correlated with suboptimal animal performance, lower profit for farmers and integrators, decreased animal welfare and well-being and increased environmental impact. Simultaneously, other factors, such as the increasing nutritional requirements due to improved modern genetics, cost-reduction and focus on sustainability, put a lot of pressure on gut health by pushing our industry towards using more circular raw materials, less antibiotics and increased animal welfare. In this article we would like to emphasize two strategies for influencing and improving gut health. One is focusing on the bidirectional interaction between a healthy microbial population and the intestinal environment and underlying gut immunity. The other is related to the physiological role of the gut, being the barrier structure, with all its functionalities and immune system. In most practical situations, this second strategy, hereafter referred to as gut integrity, seems to be primordial for preventing further development of intestinal disorders.

The intestinal barrier is a complex system that consists of tight epithelial cells, a mucus layer and gut immunity to prevent harmful pathogens and toxins from entering the bloodstream. Moreover, gut integrity implies a full development and proliferation of the epithelial barrier, so that it is able to produce sufficient digestive enzymes, absorb nutrients and restore physical damage to the gut barrier. As this structure is only one cell thick, its integrity is easily compromised, which leads to increased intestinal permeability (leaky gut), pathogenic colonization and systemic inflammation. Hereby, for many challenges in the animal industry, the underlying cause is an impaired gut integrity. Hence, protecting a healthy gut barrier should be a priority before you try to steer or modify the gut microbiome. Furthermore, every individual animal or subspecies has its specific gut microbiome, while the intestinal structure is similar. Hence it is complicated to steer the gut microbiome of the entire flock or herd towards the same optimal outcome.

To elaborate on the importance of gut integrity, let’s highlight two important challenges in animal husbandry. Firstly, weaning is a crucial step in the life of pigs. They are removed from the sow, put in a new group and given solid feed for the first time. This is highly stressful and leads to intestinal dysbiosis and post-weaning diarrhea in the first days after weaning. Stress lowers feed intake, stomach acid production and triggers inflammation. Piglets need to eat to stimulate stomach functioning and digestive enzyme production. Hence stress after weaning lowers nutrient digestion and especially protein digestion. Next, undigested protein can be fermented in the hindgut leading to pathogenic growth, i.e. ETEC, and diarrheal incidence. In other words, insufficient protein digestion is usually the triggering factor for post-weaning diarrhea. Consequently, improving gut functioning and increasing feed intake as soon as possible after weaning is crucial to overcome this challenge.

Secondly, heat stress is an environmental stressor that has an impact on gut health by inflammation and lowering gut integrity. On the one hand, the stress response results in pro-inflammatory signals that cause intestinal damage. On the other hand, the lower blood flow to internal organs increases oxidative stress and results in ROS formation. This leads to the destruction of tight junction proteins and a leaky gut. Moreover, heat stress decreases the antioxidant response in other animal body cells (e.g. liver), including decreased expression of antioxidant enzymes. In conclusion, the impact of heat stress on gut health can be lowered by improving gut integrity and lowering oxidative stress in the intestinal tract.

HOW NUTRITION INFLUENCES GUT INTEGRITY
Gut integrity is heavily influenced by animal nutrition. Especially in modern farm practices, the root cause of intestinal disorders is via suboptimal feed formulations. Local economic challenges put a lot of pressure on least-cost formulations resulting in substitutions of high-quality ingredients with local and cheaper byproducts. This comes with a risk of nutrient digestion, antinutritional factors and/or external factors like micro-organisms and mycotoxins. These risks can impair the integrity of the gut, by generating inflammation and destroying the tight junction proteins. Hence optimizing feed formulations for protein, fat and starch digestibility and monitoring antinutritional factors and mycotoxins are essential. Apart from the formulation, the budget for supplementing feed additives might also be limited. Unfortunately, intestinal health is such a wide topic that a lot of feed additives claim intestinal health benefits. Therefore, it is not easy for nutritionists to compare one with another. A wide range of additives, i.e. essential oils, probiotics, prebiotics, focus on antibacterial effectivity or steering the gut microbiome to control common gut health problems. However, there are only a few options that target gut integrity directly, i.e. SCFA, like butyric acid, antioxidants, functional amino acids and certain minerals, like zinc. From this selection, butyric acid is most interesting as this SCFA has an influence on all aspects of the gut barrier. Hereby, it is a necessary basis to achieve overall gut health in animals. Butyrate aids in gut development for young animals and in maintaining it in adult animals. On top of this, it can be combined with the above-mentioned feed additives that focus on the gut microbiome for a total solution.

BENEFITS OF BUTYRATE ON GUT INTEGRITY
The benefits of butyric acid on gut health are numerous. In summary, they can be categorized into 3 groups of action, namely: nutrient efficiency, modulation of immunity and indirect antimicrobial action. Next to intestinal health, more and more human research suggests that butyric acid ameliorates liver functioning and cardiovascular diseases. All these functions originate from a local effect as 95% of the available butyric acid is utilized by the epithelial cells and gut associated immune system. Only a small percentage reaches the liver and might enter the bloodstream. Intestinal absorption occurs mainly via transporters, either via protons or sodium coupled transport. Within the epithelial cells, butyric acid is metabolized into ATP and used as a direct energy source. Moreover, immune cells have specific receptors for butyric acid resulting in anti-inflammatory or immune modulating effects.

Firstly, when epithelial cells have more energy their proliferation and differentiation increases resulting in longer villi and more digestive enzyme production. In practice, this results in rapid intestinal development in young animals and persistent nutrient digestion and absorption in older animals, for example calcium absorption in laying poultry species.

Secondly, butyrate downregulates inflammation by strengthening the gut barrier with tight junction’s proteins and by modulating the immune response. Butyrate is known to stimulate the specific immunity and to prevent the non-specific immunity from overreacting. Next, butyrate can induce regulatory T-helper cells which have a central role in suppressing inflammatory responses. Butyrate is also known for inducing an early maturation of the immune system, which is vital for preventing intestinal diseases in young chickens and piglets.

Thirdly, butyrate has an indirect antimicrobial function. The antibacterial effect is low compared to other SCFA or MCFA, but butyric acid upregulates the host primary defense responses for production of antimicrobial peptides. Simultaneously, butyric acid creates unfavorable conditions by changing the local pH in the hindgut. Moreover, one specific mechanism in Salmonella is studied extensively. Butyrate can alter the bacteria’s genetic expression resulting in less transcription of ‘invasion’ genes. This lowers Salmonella’s ability to invade and colonize its host. In practice this results in lower shedding of the bacteria, but not in eradicating it from the intestinal tract.

THE IMPORTANT ROLE OF BUTYRATE IN BROILERS AND PIGLETS
The speed at which broilers are raised comes together with various intestinal challenges, ranging from immunity, absorptive and digestive capacity to intestinal dysbiosis. The fact that butyrate has a positive influence on all these aspects makes it an almost necessary solution throughout the production cycle of these animals. Butyrate stimulates the adaptive immune response, which is vital for broilers who start with just some maternal immunity. On the other hand, butyrate reduces inflammation, which is a universal response to all stress factors broilers must deal with. Moreover, broilers must deal with a continuous high feed intake, and thus absorptive capacity is crucial to achieve their genetic potential. Simultaneously, opportunistic pathogens, for example Salmonella, are waiting in the gut microbiome to generate dysbiosis and disease. Butyrate limits the virulence of this bacterium by modifying its genetic expression and strengthening the host’s defense responses.

Butyrate is naturally present in the hindgut of broilers by bacterial fermentation, but for intestinal development and gut integrity it should be administered via feed to target the small intestinal part from duodenum up until ileum. Usually, butyric acid is supplemented as fat coated salts of butyric acid at a dosage of roughly 500 – 1500 g/T in poultry diets depending on age, species and farm conditions. An experimental trial with 720 Ross® 308 broilers showed that supplementing 1500-1000-500 g/T BUTIFOUR® CCB in broiler diets increased villus length and eventually final body weight significantly.

Figure 1. Butifour® CCB improves villi development and zootechnical performance in broiler chickens.

Weaning is a crucial step in the life of pigs. As described above this is coupled with intestinal dysbiosis and post-weaning diarrhea in the first weeks after weaning. The best management strategy is to stimulate feed intake, thus overcoming the weaning dip, and creating a healthy gut with a developed immune system and gut microbiome. Butyrate fits in both categories. All above mentioned effects, i.e. promotion of the intestinal barrier, modulation of the immune system, improving digestion and absorption of nutrients, contribute to lowering weaning diarrhea, while the typical odor of butyrate stimulates feed intake by the piglets.

Figure 2. Butifour® CCB improves body weight and reduces diarrheal incidence in weaned piglets.

In conclusion, the use of a butyrate source in starter diets is common. Moreover, butyrate can be combined with other short or medium chain fatty acids for total antibacterial protection. The advised dosage is 750 -500 g/T for piglet starter diets or double the dosage depending on the farm conditions. A trial in an experimental farm in Belgium showed a dose response on body weight at day 49 of age, when piglets were supplemented with 750-500 g/T or 1500-1000 g/T BUTIFOUR® CCB. Another trial with weaned piglets showed an improvement of the fecal score indicating less weaning diarrhea problems. Weaning diarrhea often starts from a (protein) digestive problem, hence this explains why butyrate improves the incidence of weaning diarrhea by improving gut integrity, nutrient efficiency and by reducing gut inflammation.

Figure 2. Butifour® CCB improves body weight and reduces diarrheal incidence in weaned piglets.

In summary, different animal species benefit from rapid intestinal development and established gut integrity as a basis for overall gut health and zootechnical performance. Since butyric acid has numerous benefits for the gut barrier function, butyrate-based additives are key ingredients in livestock diets for a healthy start and prolonged productivity.

About Arno Duchateau
Arno Duchateau is a master in bioscience engineering who graduated in 2019 at the University of Leuven (Belgium). Since 2020, he has been working as Global Product Manager in the specialty feed additives division at Impextraco focusing on gut health and mycotoxin solutions. Here, he provides technical support to business partners, customers and colleagues as well as managing different product brands from development to marketing and sales.