Are peptides the missing link in protein nutrition? Part 2.

Mode of action of peptides

8 Min Read
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In recent years there has been a growing interest in the role of peptides in animal nutrition, as it has become over a $25 billion industry for the human pharmaceuticals industry. Through chemical, enzymatic, or microbial hydrolysis of proteins, whether they are animal or plant sourced, are ideal methods to generating high-quality small or large peptides that can be utilized in animal diets.

These resulting peptides could be of great nutritional and physiological value to the animal. There is mounting evidence that these manufactured bioactive peptides could enhance performance and health in livestock. Many of the standard protein-rich feedstuffs can now be transformed into value-added bioactive peptides that ultimately can improve sustainability of animal agriculture systems.

This review will focus on the nutritional and physiological or bioactive modes of action of peptides that are or can be implemented within animal nutrition programs to enhance both performance and well-being of livestock.

Amino acid absorption efficiency

Peptides are essential for protein and amino acid absorption within the gastrointestinal tract. The majority of AA transporters (Table 1) are specific in nature and there is a potential competitive inhibition of absorption between AAs, energy consuming and rate limiting. Whereas there are a variety of transporter systems for peptides that are active, transcellular and paracellular in nature, (Table 2) which do not compete or require specific AAs.

For instance, research has shown that certain peptide molecules can also stimulate AA transporters, making them more effective in transporting AAs in vitro (Wenzel et el). Whereas, in the live pig, research has also proven that peptide plus amino solutions being administered to pigs resulted in a faster and greater absorption of AAs than only administering a free AA solution (Rerat 1988, 1989). These same studies found the ceiling of AA absorption was lifted when peptides were present. This benefit is also seen in poultry whereas Ravindran et al. (2009) demonstrated that the absorption of threonine, serine, glycine, tyrosine and cysteine in broilers was linearly increased, while the remaining AA and nitrogen were quadratically increased as the level of dietary peptides were increased in diets of broilers. Thus, there is mounting evidence indicating the value of feeding peptides in conjunction with free AAs to enhance overall protein digestion and efficiency.

Table 1: Amino acid transporters

Amino acid transporter

Responsible amino acid(s)

System A (Alanine) is a symporter (NaC)

Small aliphatic amino acids

System ASC NaC symporter

Alanine, serine and cysteine

System L, not a NaC symporter

Leucine, branched chain and aromatic amino acids

System yC is not NaC dependent

Dibasic amino acids

System X-AG NaC dependent

Dicarboxylic amino acids

System B or B0 NaC symporter

Broad specificity of amino acids

System b 0+

Arginine, lysine

 

Table 2: Peptide transporters and absorption1

Type of absorption route

Active transport

  PepT1 (mostly in GI track)

  PepT2 (in tissues, blood vessels, organs, brain)

Transcellular absorption

  Endocytosis

  Penetration of lipid bilayer

Paracellular movement

  Simple diffusion

1 Adapted from Gilbert et al., 2008.

Additionally, there has been an increase emphasis within animal nutrition on reducing crude protein levels of diets while maintaining essential AA requirements via synthetic AAs. However, lowering crude protein too drastically can result in poorer performance and efficiency. But a study in growing pigs suggested that reducing crude protein can be offset by supplementing essential AA as protein bound or as peptides than as crystalline aa (Che et al., 2017). Furthermore, the value of peptides is not only found in monogastric species, but also within ruminants it suggested that microbial growth of the rumen is optimized when AAs are provided in combination with peptides, rather than supplied as a specific limiting AA (Argyle and Baldwin, 1989).

Bioactive peptides

The definition of a bioactive peptide (Table 3) is a peptide that has a biological function beyond their nutritional value of AAs, protein or nitrogen. Many bioactive peptides range from two to 20 AAs in length, but there are also some that can be greater than 20 AAs in length. These bioactive peptides can help the animal perform better, but also the ability to resist heat or other environmental stressors, have a faster recovery from an infection or disease, aides in a faster maturation of the microbiome and alleviates diarrhea. Within human pharmaceuticals, these bioactive peptides are being synthetically created for new medicines and treatments of different disorders but can also be naturally occurring in commercially available peptide products sourced from animal byproducts and plant-based proteins. Within livestock they can lead to the reduction of antibiotic use, a tool to decrease nitrogen and mineral emissions, all while decreasing feed costs.

Table 3: Examples of common bioactive peptide sequences and their functions

Type

Sequence

Function

IGF-I

SER-ARG-VAL-ARG-ARG-SER-ARG

Part of the growth hormone feedback loop

IGF-2

GLY-TYR-GLY-SER-SER-SER-ARG-ARG-ALA-PRO-GLN-THR

Part of the growth hormone feedback loop

EGF

MET-HIS-ILE-GLU-SER-LEU-ASP-SER-TYR-THR-CYS

Encourage epidermal cells division

Immune modulator

THR-LYS-PRO-ARG

Immunomodulation, such as mobilization of immune cells (T, B and innate immune cells)

Phosphopeptide

ARG-GLU-LEU-CLU-GLU-LEU-ASN-VAL-PRO-GLY-GLU-VAL-SER-SER-SER-GLU-SER-ILE-THR-ARG

Chelate multiple positive charge minerals and increase their absorption

Endotoxin inhibitor

LYS-THR-LYS-CYS-LYS-SER-LEU-LYS-LYS-CYS

Neutralize toxicity of bacterial endotoxins

Antimicrobial peptide

GLY-LEU-ILE-CYS-GLU-SER-CYS-ARG-LYS-ILE-ILE-GLN-LYS-LEU-GLU-ASP-MET-VAL-GLY

Direct inhibition of bacterial growth

Fibroblast growth factor

PHE-ASN-LEU-GLY-ASN-TYR-LYS-LYS-PRO

Stimulates tissue and blood cell growth

Exorphine

TYR-PRO-PHE-PRO-GLY-PRO-ILE-ALA-PRO-ASP-SER-LEU

Binding to opiate receptors in GI track or throughout the body

 

Feed intake enhancement

Some common feed attractant peptides include glycine-glycine, glycine-histidine-glycine and glycine-glycine-histidine peptides. However, feed flavoring agents are becoming even more advanced whereas they are being developed or synthesized to mimic natural aromatic peptides that neonates are exposed to early in life, originating from either the placenta or milk of their mothers. These compounds have special odorous attributes but also have specific taste receptors both in the mouth and gastrointestinal tract. 

An example of this is that in piglets weaned from sows fed a porcine peptide product and then fed the same product post-weaning, had an increased average daily feed intake in the starter phase post-weaning (Figueroa et al., 2016). Other ways peptides can influence feed intake are via exorphin peptide structures, such as cholecystokinin, that would bind to the opiate receptors that would evoke the intake response via peripheral binding or possibly worst case evoke anorexia via central nervous system binding.

Antimicrobial peptides

Antimicrobial peptides are the main bioactive peptides that have been researched in veterinary medicine. The two families of AMP that have been researched the most in the veterinary medical fields — defensins and cathelicidins — are known as cationic peptides. Unlike traditional antibiotics, these peptides do not work directly on the bacteria, but rather the innate immune system of the animal, to enhance immunity. One such study found that feeding a mixture of these cationic peptides to pigs improved average daily gain, even in the face of Salmonella, while reducing some fecal shedding and infiltration of Salmonella into the organs (Genovese, 2010). Furthermore, there are numerous other research publications demonstrating not only performance benefits, but improvements in nutrient digestibility, intestinal morphology and fecal microflora in pigs (Xiao et al. 2015).

Summary

The recent interest is growing in respect to both protein and AA utilization in livestock, but also novel opportunities to enhance performance and well-being of our livestock. Through the different modes of action, the utilization of peptides in nutritional programs has the ability to optimize performance while also giving us alternative solutions for sustainability. The opportunity to further reduce our crude protein levels or specialty feed ingredients in our diets is one avenue of opportunity. But also finding a peptide that can enhance the animal's own immune system to fight off disease versus the current treatments with antibiotics is another promising opportunity for the future of a sustainable meat supply.

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