Introduction

Gut: The First Line of Immune Defence
The intestinal defence system consists of several interconnected components, including the mucus layer, intestinal epithelial cells, tight junctions, antimicrobial substances, gut microbiota and gut-associated lymphoid tissue (GALT).

The epithelial cells form a physical barrier between the intestinal contents and the internal tissues. Tight-junction proteins such as occludin, claudins and ZO-1 regulate the movement of substances between epithelial cells. The mucus layer provides an additional protective environment, while immune cells located within and beneath the intestinal mucosa continuously monitor microbial and dietary antigens.
Thus, the intestine acts as both a selective absorption system and an immune surveillance system.

Gut Microbiota and Immune Development
The intestinal tract contains a complex microbial ecosystem. A balanced microbial population can contribute to pathogen exclusion, production of microbial metabolites, maintenance of intestinal integrity and modulation of host immune responses.
Beneficial microorganisms and their metabolites communicate with intestinal epithelial cells and immune cells. Among these metabolites, short-chain fatty acids (SCFAs) such as acetate, propionate and butyrate are particularly important because they can influence epithelial health, immune-cell activity and inflammatory responses. Therefore, gut microbiota and immunity have a bidirectional relationship. A healthy microbiota supports a healthy intestinal barrier and balanced immune signalling. At the same time, the immune system regulates microbial populations and helps maintain intestinal homeostasis.
What Happens When Gut Health Is Compromised?
Commercial poultry are exposed to several factors capable of disturbing gut integrity, including coccidiosis, bacterial pathogens, mycotoxins, heat stress, poor water quality, nutritional imbalance and dysbiosis.

A compromised gut can result in epithelial damage, disruption of tight junctions, increased intestinal permeability, inflammation and oxidative stress, altered immune response and reduced performance. This process is sometimes described as increased “intestinal permeability” or “leaky gut.”

When intestinal integrity is compromised, nutrients may not be utilized efficiently and microbial products can interact more extensively with host immune mechanisms. The bird may consequently spend additional nutrients and metabolic resources on inflammation and tissue repair rather than growth or egg production.

Coccidiosis, Mycotoxins and Heat Stress

Coccidiosis is a classic example of the gut–immune relationship. Eimeria infection damages intestinal epithelial cells, alters intestinal morphology and stimulates an inflammatory and immune response. Consequently, coccidiosis control is not only a parasite-management issue but also a gut health, nutrition and immune-management issue.

Similarly, mycotoxins can affect intestinal integrity, oxidative status, microbial balance and immune function. Their impact may therefore extend beyond the feed itself to the overall gut–immune axis.

Heat stress is particularly important in tropical poultry production. Heat stress can alter feed intake, intestinal physiology, microbial balance and barrier integrity, potentially increasing inflammatory and oxidative stress. Maintaining gut integrity during heat stress is therefore an important component of maintaining flock resilience.

Gut Health and Vaccine Response
An effective vaccination program depends on the bird’s ability to recognize antigens and develop appropriate humoral and cellular immune responses. This requires adequate availability of energy, amino acids, vitamins, minerals and antioxidants. Therefore, gut health indirectly supports the nutritional foundation required for immune responses. A healthy intestine facilitates nutrient digestion and absorption, while intestinal inflammation or damage can increase nutrient requirements for tissue repair and immune activity. It is important, however, to recognize that good gut health alone does not guarantee vaccine success. Vaccine quality, administration, maternal immunity, biosecurity, disease pressure, nutrition and environmental conditions also influence the final immune response.

Nutritional Support for the Gut–Immune Axis
Nutrition is one of the most important tools for supporting the gut–immune relationship. Zinc contributes to epithelial integrity, cellular proliferation, enzyme activity and immune-cell function. Selenium is an important component of antioxidant defence systems and supports cellular protection and immune function. Vitamins A and E also contribute to mucosal integrity, antioxidant protection and immune responses.
Nutritional interventions such as probiotics, prebiotics, postbiotics, organic acids, enzymes, yeast-derived products, MOS and β-glucans may be used as part of integrated gut-health programs. MOS can support gut health through microbial interactions and pathogen-exclusion mechanisms, while β-glucans can interact with innate immune pathways and influence immune-cell activity. However, responses depend on product source, structure, dose, bird age, diet and challenge conditions; therefore, these products should be evaluated based on scientific evidence and field performance rather than assuming that all products have identical effects.

Practical Approach for Commercial Poultry
A successful gut-health program should not depend on a single feed additive. It should combine:
– High-quality and properly stored feed
– Regular mycotoxin monitoring and management
– Good drinking-water quality and sanitation
– Effective coccidiosis control
– Appropriate vaccination and biosecurity
– Heat-stress management
– Balanced amino acid, vitamin and mineral nutrition
– Appropriate use of probiotics, prebiotics/postbiotics and other gut-health products
– Monitoring of litter quality, feed intake, FCR, mortality and flock uniformity

Conclusion
The gut and immune system should be viewed as two interconnected components of the same biological defence network. A healthy intestinal microbiota, intact epithelial barrier and properly functioning GALT provide the foundation for balanced immune development and response. For commercial poultry, the concept is simple: “Protect the gut to support immunity, and support immunity to maintain flock resilience.”
Gut health is therefore not only about digestion and FCR. It is closely connected with nutrient utilization, immune development, disease resistance, vaccine responsiveness and ultimately flock productivity.
The future of poultry nutrition will increasingly focus on managing the gut–microbiota–immune axis through integrated nutrition, health and farm-management strategies rather than addressing individual problems in isolation.

Yet despite the widespread use of organic trace minerals (OTMs), one important misconception continues to exist in the industry: that all organic trace minerals are the same.

Looking Beyond Inclusion Levels
When evaluating trace mineral programs, discussions often focus on inclusion rates, mineral concentration, and cost per ton of feed.

However, the true value of a trace mineral is not determined simply by how much is added to a formulation. Rather, it is determined by how much of that mineral is available for absorption and utilization by the bird. This distinction becomes increasingly important in modern poultry production.

Many producers experiencing challenges like, inconsistent performance, reduced meat quality, or variability in the flock focus on nutrient inclusion. Yet nutrients can only contribute to biological functions if they successfully reach the absorption sites where they are needed.

As poultry genetics continue to advance, nutritional efficiency has become just as important as nutritional adequacy. This shift is causing nutritionists to move beyond a simple question of: “How much mineral is in the feed?” to a more important question: “How much mineral is actually available to the bird?”

Understanding the Challenge: Mineral Antagonism
Trace minerals perform important functions throughout the bird’s body. Zinc, copper, and manganese act as cofactors for numerous enzymes involved in bone formation, connective tissue development, collagen synthesis, skin integrity, antioxidant defense, and immune function.

However, the digestive tract is a highly complex environment. As minerals move through digestion, they encounter changes in pH and interactions with dietary compounds such as phytate, fiber components, and even other minerals. These interactions can reduce mineral availability before absorption occurs.

This phenomenon, referred to as mineral antagonism, helps explain why increasing mineral inclusion does not always result in improved mineral utilization. Simply feeding more minerals does not necessarily mean the bird receives more minerals. In many situations, the challenge is not supply. The challenge is bioavailability.

Dietary antagonisms can reduce mineral availability before absorption occurs, limiting nutrient utilization despite adequate inclusion levels

Organic Trace Minerals: A Category, Not a Chemistry
To help improve mineral bio-availability, the industry increasingly adopted organic trace minerals. However, the term “organic trace mineral” can create confusion. Some assume that all OTMs provide similar benefits because they belong to the same category. In reality, organic trace minerals represent a broad group of products that may differ substantially in:
· Ligand type
· Ligand-to-mineral ratio
· Molecular structure
· Bonding characteristics
· Electrical charge of the molecule
· Stability in Upper Digestive Tract
These differences influence how minerals behave in the gastrointestinal tract and how effectively they remain available for absorption. In other words, two products may both be labelled as organic trace minerals while functioning very differently inside the bird.

Why Chelation Matters
Among organic trace minerals, one class stands out from the others: bis-chelates. The word chelate originates from the Greek word chela, meaning crab claw or pincer. Similar to two crabs holding a metal securely giving it the maximum protection a Chelate forms when a ligand connects to a metal atom at more than two points. A 2 five member rings connected to the metal with two points of contact is the most stable complex found in nature. This structure helps provide protection compared with less defined mineral associations. However, not all organic trace minerals are true chelates. True chelates require a neutral charge to protect the mineral and enhance stability. Not all organic trace minerals (OTMs) provide a neutral charge; therefore, not all OTMs are true chelates. Some products are better described as complexes, proteinates, or other association forms. While they are still classified as organic trace minerals, they can differ significantly in chemical stability and behavior during digestion. The degree of protection provided by the mineral structure ultimately determines how vulnerable the mineral may be to antagonistic interactions.
Differences exist among chelates, too. There are chelates where one ligand is bound to the metal and then there are bis-chelates where two ligands are bound, creating a neutral charge and making the molecule less susceptible to antagonism. (see image)

Why Molecular Structure Matters
Research continues to demonstrate that mineral structure influences stability and bio-availability. When minerals dissociate during digestion, they become charged ions that are more likely to interact with negatively charged compounds such as phytate, fiber complexes and other minerals. These interactions can reduce availability before absorption occurs.

For this reason, increasing attention is being given to mineral structures specifically designed to maintain stability throughout digestion. One such approach is bis-chelation technology.

Bis-chelated trace minerals are characterized by a defined molecular structure consisting of one mineral ion bound to two ligands, creating two stable chelate rings. This unique architecture helps maintain structural integrity while moving through the digestive tract.
An equally important feature is their neutral molecular charge. Because neutrally charged molecules are less likely to participate in unwanted interactions, the structure helps protect the mineral, reducing opportunities for antagonism and supporting mineral availability until absorption occurs.

Bis-chelated trace minerals feature a defined molecular structure designed to support stability and mineral availability during digestion.

The Future of Trace Mineral Nutrition
As poultry production evolves, mineral nutrition must evolve with it. The industry’s next opportunity may not come from increasing mineral inclusion rates but from improving how effectively minerals are utilized by the bird. This requires looking beyond product categories and focusing on the scientific characteristics that influence mineral availability. Organic trace minerals can provide significant advantages over traditional inorganic sources. However, not all organic trace minerals are created equal. Their molecular structure matters. Their stability matters. And ultimately, their ability to deliver minerals to the animal matters.

As nutritionists continue searching for ways to improve performance consistency, skeletal integrity, meat quality, and return on investment, bis-chelated trace minerals are an increasingly important technology because they combine defined structure, enhanced stability, and optimized bioavailability into a scientifically designed mineral solution.

Contact your local NOVUS representative to learn more about bis-chelated trace minerals from the company that brought the technology to the animal agriculture industry over 20 years ago.

Introduction
Poultry nutritionists must search for ways to lower the overall cost of feed as the price of dietary energy sources continues to rise steadily. As a result, they have at times opted to incorporate lower-quality energy feed ingredients as a solution to this problem. These methods may cause the birds to perform poorly in terms of feed conversion ratio, body weight gain, and overall low productivity. Feathered creatures are by nature omnivores that are designed from an early age to consume both plant and animal materials. But for several reasons, the diet of chickens is increasingly changing to a vegetarian diet. This change caused the loss of some important entities, such as creatine, a key substance in meat that is not found in plants. Creatine is a crucial compound for cellular energy production. Creatine phosphate is the primary substance responsible for supplying ATP, the cell’s energy source. When creatine is not obtained through diet, the body’s creatine levels decrease and must be replenished through endogenous amino acid synthesis. Poultry farming has experienced significant growth in recent years, with poultry production increasing by nearly four times since 1957. This growth has been primarily driven by the rise in carcass (+12%) and breast meat production (+50%). What if we could enhance embryo development by providing a readily available energy source to improve hatchling survival and the first days of life? This can be achieved by supplementing broiler breeders with creatine. Creatine enables muscle cells to generate additional energy by converting low-energy ADP back into ATP. While creatine is naturally present in muscle tissue and animal-derived foods, the concentrations in animal proteins can vary widely due to the quality of raw materials and the instability of creatine under harsh processing conditions. Moreover, animal protein is seldom included in animal feed, as most bird feed is composed of plant proteins and grains.

Benefits of Creatine Forerunner
Even though birds have the ability to produce their own creatine, the amount generated is insufficient to meet the demanding growth and performance needs of modern broilers. The early stages after hatching are crucial for the development of efficient broilers, as they require a significant amount of energy. This is why creatine plays a vital role in this process. While creatine can be transferred from the hen’s diet and synthesis to the egg, the levels passed on are typically low. By supplementing broilers with creatine, we can ensure that the embryo receives an additional energy reserve that can be utilized post-hatching. However, creatine is sensitive to heat and can be lost during the preparation of bird feed supplements.

A strategic solution is to include the creatine precursor guanidinoacetic acid (GAA) in the mix, which supports optimal nutritional conditions. GAA is converted to creatine in the liver and stored in muscle tissue, making it a valuable addition to animal feed for broilers.

Effects of Maternal Nutrition on Hatchability
New research from Israel has revealed significant findings that support the transfer of creatine from chicken to chicken when GAA (creatine precursor) is added.
Some research indicates that supplementing broilers with GAA may impact the accumulation of creatine in laying hens. The addition of GAA to chicken feed has been proven to boost the creatine levels in both egg yolk and albumin, with the most noticeable impact seen in the yolk, which is crucial for embryo development. By including dietary GAA (0.15%), the creatine content of the entire egg can be increased by over 40%.

GAA: What does it ENTAIL?
Natural amino acid derivative guanidinoacetic acid (GAA) is widely known for its pivotal function in the manufacture of creatine, a vital substance involved in the metabolism of cellular energy. GAA, sometimes referred to as betacyamine or glycocyamine, has been studied as a dietary supplement for increasing energy. In vertebrate animals, GAA is the sole direct precursor that produces creatine. Glycine and arginine are the building blocks for the synthesis of GAA, a metabolic intermediate product that is mostly produced in the kidney and pancreas. GAA is converted to creatine by methylation once it reaches the liver. In the creatine biosynthesis pathway, the primary regulated and rate-limiting step is the synthesis of GAA from arginine and glycine. Interestingly, this synthesis is accomplished in different organs, the first step (synthesis of guanidinoacetic acid from arginine and glycine) taking place in the kidney, the second one (synthesis of creatine from guanidinoacetic acid) in the liver. Thus, guanidinoacetate is synthesized in the kidney, and then transported to the liver where it is converted to creatine, which is then transported to its destination organs.

GAA Biosynthesis
The synthesis of guanidinoacetate requires two amino acids, arginine and glycine. Arginine transfers its amidino group to the amino group of glycine to produce ornithine and GAA, catalyzed by L-arginine: glycine amidino transferase (AGAT). Guanidinoacetate is then methylated by the methyl group of S-adenosylmethionine (SAM), which is synthesized from methionine. This reaction produces creatine and S-adenosylhomocysteine ​​(SAH) and is catalyzed by guanidinoacetate N-methyltransferase (GAMT). Creatine synthesis is an inter-organ metabolic process, with GAA synthesis occurring primarily in the kidney and GAA methylation occurring primarily in the liver. The addition of GAA for creatine synthesis imposes a methylation demand on the body because creatine synthesis is considered to be the major user of methyl groups from SAM (S-adenosyl methionine). Thus, methyl group of betaines can be used in transmethylation reactions for synthesis of creatine and may reduce the requirement for other methyl group donors such as methionine and choline. Betaine is an osmolyte that helps maintain cellular water homeostasis and serves as a methyl group donor, which are its two main metabolic functions. It has been shown that the antioxidant mechanism of betaine strengthens non-enzymatic antioxidant defenses.


Appropriate GAA Dose
The growth performance of broiler chickens may be successfully enhanced by dietary supplementation of 600-1200 mg/kg GAA. The lowest dose required to boost performance is 600 mg/kg GAA. GAA concentrations up to 1500 mg/kg feed did not affect broiler performance or mortality; However, at 3000 mg/kg feed, food intake and body weight decreased somewhat, although not significantly. Feed intake was significantly affected by the highest level of inclusion (6000 mg GAA/kg feed), resulting in a significant reduction in weight gain. GAA treatment had no apparent effect on mortality or feed efficiency.

Why is GAA Used?
· As a creatine precursor GAA plays an important role in energy metabolism.
– However, due to the instability of creatine in the production process and cost, GAA has been studied as an effective alternative to creatine supplements.
– GAA has been tested as a potential feed additive to improve energy utilization and growth performance in poultry.
– GAA has been combined with methionine to improve growth performance and may also act as an arginine sparing agent in birds.
– GAA supplementation increases growth, reproductive performance and meat quality in poultry.
– Among its many proven benefits, GAA effectively improves feed conversion ratio and animal performance.
– GAA has many roles outside of creatine, including stimulation of insulin secretion, neuromodulation and vasodilation.
– Supplemental GAA improves growth performance in heat-stressed chickens.
– Cold stress is another physical environmental stress that hugely impacts the poultry industry. During commercial broiler production, cool temperatures are the primary cause of ascites and related deterioration of growth performance. Dietary inclusion of 1.2 g/kg GAA and betaine improved FCR in broilers under cold stress, suggesting GAA can be used as an efficient supplement to improve the harmful effects of cold stress in broilers.
– Furthermore, GAA can be utilized as a feed supplement in intensive rearing systems to improve feed efficiency and minimize myopathies in the pectoral muscle.
– Supplemental GAA can be used to enhance the fertility rate and sperm penetration in aged broiler breeder hens, possibly by increasing ATP availability in sperm mitochondria, thereby increasing sperm motility and fertility rate.
– Another way that has the potential to increase the productivity of native chickens is to use betaine. Betaine has an effect as a methyl donor for methionine and its diverse physiological properties can improve the intestinal environment and increase the ability of feed absorption. Accumulation of betaine in cells may protect against osmotic stress.
– GAA is known to have an antibacterial effect.
– GAA is safe and potentially efficacious in poultry nutrition, supporting growth in chickens for fattening.

Conclusion
There is a growing body of research dedicated to determining the most effective methods for feeding day-old chicks in order to ensure they develop into healthy, rapidly growing birds. Solutions range from providing small, easily digestible feed pellets to utilizing specially designed feeders that allow young chicks to access their food with ease. Enhancing the nutritional content of eggs with creatine to better align with the physiological needs of modern broilers is a crucial step towards enhancing broiler production in terms of health, growth, and efficiency. Recent studies on using GAA as a creatine source have shown that incorporating GAA into the diet of broiler breeder hens is a practical and efficient approach to achieving this goal.