From Ingredient Selection to Molecular Bioavailability


In recent years, the quality standards of foods intended for dogs and cats have undergone changes and redefinitions. While for decades, one of the most attractive aspects of commercial diets was the use of premium meats or exotic protein sources, the current focus has shifted toward the nutrients present in each ingredient and their bioavailability within the diet. 
 

Advances in animal nutrition studies have encouraged a more precise and effective approach, based on the principle that animals do not require specific ingredients, but rather essential nutrients in adequate amounts. This redefinition in ingredient selection represents a movement toward maximizing nutritional efficiency, with a focus on greater nutrient bioavailability, contributing to the health and well-being of companion animals.


Why Protein Size Matters
The molecular structure of food is important because the immune system interacts with dietary proteins through the recognition of epitopes—mechanisms that are still not fully understood—formed by specific amino acid sequences present on the surface of large polypeptides. In sensitized animals, these proteins may bind to immunoglobulin E present on the surface of mast cells, triggering a cascade of inflammatory mediators that results in the clinical signs of adverse food reactions, such as intense pruritus and gastrointestinal alterations.

For a long time, the strategy used to address this condition was the search for different proteins, derived from novel sources to which animals had not yet been exposed and, therefore, would have a lower probability of previous sensitization. However, ensuring this 'novelty' and the constant risk of cross-contamination make this approach increasingly difficult and less reliable, being effective only in some cases.

Hydrolysis: The 'Molecular Disguise' of Proteins
Advances in animal nutrition have prioritized the so-called 'molecular disguise' of conventional proteins through partial or extensive enzymatic hydrolysis, which essentially is the structural modification of proteins through hydrolysis.

The hydrolysis process promotes the breakdown of intact proteins, generally with molecular weights between 15 and 70 kDa, into small peptides and free amino acids, reducing their molecular weight to values below the threshold of immune recognition. In this way, the antigenic 'target' of immunoglobulins is minimized without significantly altering the nutritional value of food.

For a protein source to be considered hydrolyzed and effective in the management of food allergies, most of its peptides should have a molecular mass below 10 kDa, with the presence of much smaller protein fractions (below 500 Da) being common. Recent characterizations illustrate the precision and efficiency of modern processes, demonstrating that several protein ingredients—from both animal and plant origins—can achieve molecular profiles with a low probability of detection by the immune system.

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Hypoallergenic and Anallergenic Diets


This has opened the opportunity for the development of hypoallergenic diets, characterized by being composed of few ingredients and often by a single protein source subjected to partial or total hydrolysis before being included in the formulation. These diets are characterized by adequate digestibility, reduced allergenic potential, and a good amino acid balance, with high bioavailability of essential amino acids.

In addition, there are purified diets, also known as anallergenic diets, in which the protein is supplied with an extremely high degree of hydrolysis, resulting in very small peptides that are practically undetectable by the immune system. Hydrolyzed diets, therefore, offer advantages for patients with deficiencies in protein digestion mechanisms or for those affected by enteropathies responsive to intact dietary proteins.


Chronic Enteropathies and Nutritional Support


Patients with chronic enteropathies present a group of gastrointestinal conditions characterized by persistent or recurrent signs, such as diarrhea, vomiting, weight loss, changes in fecal quality, and reduced intestinal absorptive capacity. In these cases, the intestinal mucosa may present prolonged inflammation, alterations in the intestinal barrier, dysbiosis, and compromised villi, which are essential structures for adequate nutrient utilization. These patients often represent a major challenge for their owners and the veterinary team, and their quality of life may be significantly compromised when effective therapeutic strategies are not established.

The advent of diets containing hydrolyzed or extensively hydrolyzed proteins represents a milestone in companion animal nutrition. These formulations are fundamental for the recovery and quality of life of patients affected by inflammatory bowel disease or other digestive disorders related to dietary proteins, as they allow the restoration of digestive function, adequate amino acid absorption, and tissue recovery, favoring weight gain, maintenance of muscle mass, and remission of clinical signs.

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Clinical Applications and Perspectives

In dogs with food-responsive diarrhea, hydrolyzed diets frequently promote rapid resolution of clinical signs as they are both diagnostic and therapeutic tools in cases of food allergy. In dogs with more complex conditions, such as inflammatory bowel disease, the use of hydrolyzed proteins is essential to minimize the development of sensitization to new dietary antigens.

The supply of 'pre-digested' peptides helps reduce the antigenic load of the diet while maintaining the animal's nutritional support, and providing the energy required for tissue repair processes. Recent studies have also explored the use of hydrolyzed proteins derived from poultry liver, feathers, viscera, fish, beef, and insects to improve fecal quality and modulate intestinal fermentation in dogs, highlighting the versatility of these protein sources in clinical settings.

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Conclusion


The transition from an ingredient-focused approach to one centered on molecular bioavailability defines modern companion animal nutrition. As our understanding of the pathophysiology of disorders affecting dogs and cats deepens, the selection of raw materials will continue to be evaluated based on their effective contribution to metabolic health.

This shift is not limited to the prevention of food allergies but seeks to optimize nutrient utilization by animals. By prioritizing adequate molecular weight, high digestibility, and modulation of the intestinal environment, the industry develops solutions that translate directly into improved quality of life for patients. The true indicator of quality lies in the ability to provide nutrients in a bioavailable, safe, and consistent way, allowing the survival of patients who previously had limitations almost incompatible with life.


By Paula K. Velho¹, Gustavo de A. Fusquine¹, Laura S. de Freitas¹, Eduarda B. F. de Oliveira¹, Luciano Trevizan¹
Source: All Pet Food Magazine

¹GENAC – Grupo de Estudos em Nutrição de Animais de Companhia da Universidade Federal do Rio Grande do Sul
 

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References
FASCETTI, Andrea J. et al. (Ed.). Applied veterinary clinical nutrition. 2012.
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MARTÍNEZ-LÓPEZ, Lina María et al. Effect of sequentially fed high protein, hydrolyzed protein, and high fiber diets on the fecal microbiota of healthy dogs: a cross-over study. Animal microbiome, v. 3, n. 1, p. 42, 2021. DOI: 10.1186/s42523-021-00101-8.
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PINTO, Caroline FD et al. Effects of hydrolyzed chicken liver on digestibility, fecal and urinary characteristics, and fecal metabolites of adult dogs. Journal of Animal Science, v. 101, p. 1-12, 2023. DOI: 10.1093/jas/skad366.
PINTO, Caroline Fredrich Dourado et al. Effects of diets based on hydrolyzed chicken liver and different protein concentrations on the formation and deamination of biogenic amines and total antioxidant capacity of dogs. Animals, v. 13, n. 16, p. 2578, 2023. DOI: 10.3390/ani13162578
SEZEROTTO, Pamela Prestes et al. Hydrolyzed chicken liver and increasing crude protein levels on palatability, digestibility, and intestinal fermentation products of cats. Journal of Animal Science, v. 103, skaf173, 2025. DOI: 10.1093/jas/skaf173.
 


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