Human Milk Proteome and Peptidome

Title: Human Milk Proteome and Peptidome

Authors: J. Zhu et al.
Published: 2021

The Journal of Nutrition

Personalized Profiling Reveals Donor- and Lactation-Specific Trends in the Human Milk Proteome and Peptidome

Each person has his or her own unique DNA. It is becoming more and more apparent, that this may also apply to our proteome -the entire set of our proteins.
Proteins are built of amino acids, which can form chains and are then called peptides. Peptides are often precursors, or the building blocks of full proteins.

The complete analysis of an individual proteome is gaining momentum, due to advancements of profiling techniques. However, such methodologies still need improvement to be used in large-scale settings, as part of individualized healthcare. Such individual assessments are of immense value as the very detailed insights can be compared against the individual’s own baseline measurement, rather than against the one of a whole population, as is currently the case.

So far, individual proteome studies have primarily focused on individual’s blood components such as plasma or serum. Yet, breastmilk has been characterized to a much lesser extent. But like blood, breastmilk may also provide a good reflection of the mother–infant health status. Breastmilk is tailor-made for the infant, as newborns not only receive all necessary nutrients but e.g. also protective factors which help to defend the developing infant against a variety of pathogens in early life.
In addition, most published studies so far have focused on proteins, neglecting research into peptides. However, several endogenous peptides can be found in human milk. Each one with their own unique functionalities. Often these peptides are derived from intact human milk proteins. By analyzing the whole proteome and peptidome, one can gain a much better understanding about the richness of human milk proteinaceous compounds. Moreover, these new analytical approaches may therefore also pave the road to assign more functional contributions to human milk proteins and peptides which might be relevant for healthy development in early life.

The Journal of Nutrition Genomics, Proteomics, and Metabolomics recently published a study led by researchers from the University Utrecht, the Netherlands Proteomics Center in Utrecht and Danone Nutricia Research. In this study the authors characterized >1300 proteins, as well as 2000 peptides in breastmilk from two recent mothers. They were analyzing multiple samples, which had been collected over a time course of 16 weeks of breastfeeding. This was accomplished to understand possible individual’s changes in the human milk proteome and peptidome over time.

Analyzing peptides and proteins to get the whole picture

By looking at both proteins and peptides, they found a much greater abundance of proteinaceous substances than described before and could identify 60 additional proteins. The authors also further investigated. Looking at both essential components -peptides and proteins- at the same time thus provides a more complete overview of the possible biological roles of these compounds during lactation. For example, possible functional implications of the identified human milk compounds do range from aiding the infants’ digestive system to protection against pathogens by a range of human milk antibodies.

Investigating the individual over time enables spotting abnormalities

The authors confirmed that each mother showed unique characteristics with regards to their overall milk profile. In addition, each individual showed gradual concentration changes of milk components as time passed by. This reflects how the composition of milk may adapt to the needs of the growing baby.

By closely monitoring each individual over time, the authors also detected a unique phenomenon. One mother or her baby likely experienced an acute inflammation/infection at week 6 during the investigation, as her milk protein and peptide composition was rather abnormal at this particular timepoint. At that point in time multiple peptides and proteins, with immunological functions, changed dramatically in abundance. This deviation in milk components did not appear earlier and was quickly resolved by itself. Anecdotally, the affected mother reported that her baby had developed a skin rash around the same time. It resolved on its own shortly after. The authors concluded that the correlation of such an abnormal milk profile and the infant’s skin rash was intriguing. Unfortunately, they could not fully establish whether there was any causal relationship between these two phenomena.

Characterizing immune components in milk

Among the critical immune components in human milk are intact antibodies and components of the so-called complement system. Antibodies reflect which pathogens the mother has already encountered and thus provide individualized protection to the newborn. Components of the complement system assist the immune response in efficiently dealing with pathogens.

The authors could detect all types of immune relevant antibodies (IgA, IgM, IgG, IgD, and IgE) and important complement components in milk from both donors. Furthermore, they detected how the concentrations of antibody classes, as well as concentration of complement components changed throughout time. This likely reflects how milk again adapts to the needs of the developing infant, optimally assisting the infant during development of his or her immune system.

Advantages of personalized milk analysis

Such detailed analysis of the human milk proteome and peptidome provides evidence that the composition of human milk is highly personalized. The author’s approach demonstrates that such profiling is now technically feasible. With further advancements in automation and data analysis, it should become possible to drastically extend personalized profiling, even frequent sampling throughout time. Such analysis will shed more light on the molecular composition of the most important source of nutrition during the early life stages of the newborn. It will unravel how exactly breastmilk changes dynamically due to interactions of the mother and the infant.

Please read the full publication here: Personalized Profiling Reveals Donor- and Lactation-Specific Trends in the Human Milk Proteome and Peptidome | The Journal of Nutrition | Oxford Academic

Human milk is the best source of nutrition for infants. Inspired by its complex composition and functionality Danone Nutricia Research has been researching this fascinating food source for over 40 years and will continue its journey to unravel its complexity.

Further reading recommendations:
Human milk proteome: what’s new?
– Quantitative Longitudinal Inventory of the N-Glycoproteome of Human Milk from a Single Donor Reveals the Highly Variable Repertoire and Dynamic Site-Specific Changes
– The richness and diversity of the human milk proteome explored by mass spectrometry