Milk-Based Bionutrient Trials to Improve Outcomes in Preterm Infants: Challenges and Opportunities

Abstract Objective  Bionutrients (or immunonutrients) are dietary components present in milk, or supplements that could be added to milk diets, that impact health and disease. With few exceptions, most of these are present in human breastmilk and the majority are also present in amniotic fluid. Study Design  Bionutrients can be proteins and peptides including enzymes, hormones, immunoglobulins, and growth factors and can also be molecules such as human milk oligosaccharides, amino acids, or lipids such as docosahexaenoic acid. Many of these have ancient origins, are found in other species, and existed before mammalian lactation evolved. Bionutrients may act in diverse ways when administered enterally: they may impact gut bacterial communities or epithelial cell metabolism, or they may pass into the lamina propria where they interact with the gut and systemic immune systems. Clinical trials have often used bovine analogs such as lactoferrin or may use artificially synthesized or recombinant compounds including insulin, bile salt stimulated lipase, or oligosaccharides. Results  Challenges arise because the bioactivity of proteins, such as lactoferrin, may be affected by processing and pasteurization meaning that the impacts of commercial products may differ. The challenge of determining the optimal bioactivity of any single preparation may be even greater in complex compounds such as milk fat globule membrane. It is also possible that bioactivity is affected by the milk matrix, that is, may differ between formula and human milk. Conclusion  Finally, it is important to appreciate that nutrients do not function in isolation, and most will not act like drugs, that is, they may take several days or longer to exert an affect. Key Points Breastmilk contains high concentrations of bionutrients and provides more than macro- and micronutrients. Bionutrients can be proteins (e.g. enzymes, hormones, or immunoglobulins) or molecules (e.g. human milk oligosaccharides or amino acids). Bionutrients can be added to milk feeds but high quality trials are needed.