Peptides in Human Milk
Peptides in Human Milk
Author: J. Bruce German, Davis
Key Messages
Milk proteins undergo digestion into peptides and amino acids within the stomach and intestine in a complex series of reactions.
Many of the peptides from milk are generated by endogenous enzymes within the mammary gland prior to secretion.
Peptides from milk proteins in turn are generated by milk’s endogenous enzymes throughout the gastrointestinal tract of the infant.
The presence of peptides in human milk is well known, and research on these components has been active for over half a century. The history of peptide research and innovation can be thought of as occurring in 3 phases. During the first period of scientific discovery and applications, milk proteins were digested by microbial proteases into peptides prior to consumption with the goal to enhance digestion and minimize immunological reactions of the intact proteins. The second phase focused on peptides released by specific proteases with explicit biological sequence and activities screened for known targets of therapeutic benefit. The third phase (just beginning) is focusing on the peptides actually produced within the intestine of breastfed infants, and research is identifying the targets of their action within infants.
Milk proteins undergo digestion into peptides and amino acids within the stomach and intestine in a complex series of reactions guided by proteolytic enzymes, physical mixing, pH shifts, and biological surfactants. Not surprisingly given the complexity, digestion can fail to reach completion both due to insufficient capacity within individuals due to immature digestive system or health conditions and to unusually resistant protein structures in the diet. If undigested, proteins and large peptides continue to flow down the intestine, fail to deliver amino acids as nourishment, can elicit autoimmune reactions notably allergies, and feed specific members of the intestinal microbial community yielding undesirable products and metabolites. In response to the documented consequences of failures in protein digestion, scientists developed strategies to predigest proteins and provide partially hydrolyzed products [1].
Some peptides released from milk have bioactive properties. Antimicrobial and antihypertensive screens were the first to yield positive results [2].
The arrival of genomics and the modern analytical methods has made it possible to identify, sequence, and annotate the protein origins of the peptides in human milk that are actually generated in vivo within the mammary gland and infant [3]. This new approach has the potential to change the entire perspective of peptide efficacy. Many of the peptides from milk are generated by endogenous enzymes within the mammary gland prior to secretion [4]. Peptides from milk proteins in turn are generated by milk’s endogenous enzymes throughout the gastrointestinal tract of the infant.
While it is not guaranteed that all peptides generated in milk evolved to provide specific biological functions, it is a compelling place to start. Their actions in human infants act as food, i.e. consumed biomaterials, reach their targets of efficacy at an effective dose, and, perhaps most importantly, do so safely. As the targets of these peptides are discovered, it will be possible to develop diagnostics to monitor those processes, new strategies, and new products. A bright future indeed.
References
1. Greer FR, Sicherer SH, Burks AW; American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics Section on Allergy and Immunology: Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics 2008;121:183–191. doi: 10.1542/peds.20073022. Review.
2. Clare DA, Swaisgood HE: Bioactive milk peptides: a prospectus. J Dairy Sci 2000;83:1187–1195. doi: 10.3168/jds. S00220302(00)749836.
3. Dallas DC, Guerrero A, Khaldi N, Borghese R, Bhandari A, Underwood MA, Lebrilla CB, German JB, Barile D: A peptidomic analysis of human milk digestion in the infant stomach reveals proteinspecific degradation patterns. J Nutr 2014;144:815–820.
4. Guerrero A, Dallas DC, Contreras S, Chee S, Parker EA, Sun X, Dimapasoc LM, Barile D, German JB, Lebrilla CB: Mechanistic peptidomics: factors that dictate the specificity on the formation of endogenous peptides in human milk. Mol Cell Proteomics 214;13:3343–3351.
