MFGM and Infant Development

MFGM and Infant Development

This summary is adapted from ‘Compositional Dynamics of the Milk Fat Globule and Its Role in Infant Development’, by Lee et al. 2018. Milk fat globule (MFG) is a component of human breast milk which has been getting attention for its potential beneficial effects on infant health. MFG is a fat released from the mammary glands surrounded by milk fat globule membrane (MFGM). MFGM is made up of many fats and proteins which have a wide range of biological roles. Roles which may be of particular importance in infants are aiding in the maturation of the gut and regulating immune function. Antimicrobial substances which form part of MFGM may have a central role in shaping the gut microbiome, which has implications for immune and inflammatory diseases in the infant. MFG is difficult to mimic in infant formulas due to its complex structure. The review summarised here aims to detail the components of MFG, its potential role in the immune system and how it may aid in intestinal maturation and microbiome establishment. The composition of MFG varies between individuals and over the course of lactation. The fat core of MFG represents approximately 98% of total milk fat and half of the infant’s energy intake1. MFG contains a wide range of fatty acids in its core. MFGM surrounds this core and is a complex mixture made up of 60% protein and 40% fat, which stabilises the globule. The composition of both the MFG and MFGM changes throughout lactation2. This may be due to the requirements of the infant, with the contents tailored to the specific concentration of the specific protein or fat that the growing infant needs. Genetic factors also influence the composition, along with maternal diet. The proteins in the MFGM make up around 1-4% of the total protein in milk3. However, some of these proteins are thought to be important for health even at these low concentrations. As there are hundreds of different proteins making up the MFGM, it has been difficult to characterise the functions of individual proteins, but some research has linked them to immune defence. The proteins of the MFGM vary throughout lactation. Postpartum days 1-7 there is a significant increase in proteins related to lipid synthesis, and a downregulation of immune regulated proteins. Levels of proteins with antimicrobial function are higher in colostrum than in mature human milk, which may aim to compensate for immature neonatal immunity. MFGM isolates which are used in infant formula are predominantly sourced from cow’s milk. It is therefore very important to understand the differences in composition between bovine and human MFGM. Human MFGM is significantly enriched with lactoferrin compared to bovine MFGM, whereas bovine MFGM has some antimicrobial substances which are not present at all in human milk, and in general have a wider range of proteins with antibacterial proteins4. Gut maturation in the infant is stimulated by the interaction between dietary components, substances secreted by the infant, and the microbiome which has colonised it. It is hypothesised that there is a ‘critical window’ of events occurring in early life which shape the microbiome in the infant and may increase or decrease the risk of disease in later life. It is therefore a priority to understand how breast milk supports the intestinal development in the best way possible. MFG may have a role in this. Human milk fats contain multiple components which aid in the development of the gut after birth. Many studies investigating the influence of MFG on this process have used animal models, which limits our ability to know the effect on human infants. However, results have been promising and certain fats such as sphingolipids and gangliosides have well established beneficial effects on gut maturation5. MFGM components may also have a role in regulating cellular events which lead to the maturation of the gut immune system. This may explain a study which showed that supplementation with bovine MFGM enhanced immunity6. It has been established that the organisms making up the gut microbiome differ distinctly between breast-fed and formula-fed infants. It has been proposed that this may be partially responsible for the differences in health between these two groups. The microbiome is progressively built after birth depending on a wide range of factors but infant nutrition is one of the most crucial. The MFG must be broken down to realise the fats and proteins which make it up, which contrasts with freely accessible vegetable fats included in infant formula. This will influence the ability of these fats to shape the microbiome in the infant. There have been a wide range of animal and some human studies on this with varying results. MFGM has been found to support the growth of beneficial bacteria in the gut in some of these studies, but the results are not conclusive. Lastly, it has been hypothesised that beneficial probiotic (live beneficial microorganisms) bacteria are able to travel from the mammary gland to the infant gut by sticking to components of the MFGM7. Bacteria found in breast milk have been known to colonise the infant gut. Some of these bacteria have been seen to adhere to the MGFM, which forms the basis of this hypothesis. MFGM in itself may also have a prebiotic (substances which encourage the growth of healthy microorganisms) effect, as it can reach the gut intact and are capable of releasing substances which encourage the growth of healthy bacteria8. This growing evidence suggests a role for MFG and MFGM in infant health, particularly for gut health as emphasised here. As these molecules are so complex, they cannot be synthesised and therefore infant formulas are supplemented with isolated bovine MFG. Bovine MFG does not function exactly as human MFG does, but still appears to have worthwhile effects particularly for the immune system. Most studies we have on the functions of MFG have been conducted in animal models, but there are a growing number of positive results from human studies. Further research on the differences between bovine and human MFG will allow for guidelines to be developed which provide the greatest benefit for the infant.

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References
  1. Innis SM. Human milk: maternal dietary lipids and infant development. Proceedings of the Nutrition Society. 2007 Aug;66(3):397-404.
  2. Vanderghem C, Bodson P, Danthine S, Paquot M, Deroanne C, Blecker C. Milk fat globule membrane and buttermilks: from composition to valorization. Base. 2010 Jan 1.
  3. Liao Y, Alvarado R, Phinney B, Lönnerdal B. Proteomic characterization of human milk fat globule membrane proteins during a 12 month lactation period. Journal of proteome research. 2011 Aug 5;10(8):3530-41.
  4. Lu J, Wang X, Zhang W, Liu L, Pang X, Zhang S, Lv J. Comparative proteomics of milk fat globule membrane in different species reveals variations in lactation and nutrition. Food chemistry. 2016 Apr 1;196:665-72.
  5. Nilsson Å. Role of sphingolipids in infant gut health and immunity. The Journal of Pediatrics. 2016 Jun 1;173:S53-9.
  6. Lee H, Zavaleta N, Chen SY, Lönnerdal B, Slupsky C. Effect of bovine milk fat globule membranes as a complementary food on the serum metabolome and immune markers of 6-11-month-old Peruvian infants. npj Science of Food. 2018 Apr 12;2(1):6.
  7. Guerin J, Burgain J, Gomand F, Scher J, Gaiani C. Milk fat globule membrane glycoproteins: Valuable ingredients for lactic acid bacteria encapsulation?. Critical reviews in food science and nutrition. 2019 Feb 21;59(4):639-51.
  8. Lee H, Garrido D, Mills DA, Barile D. Hydrolysis of milk gangliosides by infant‐gut associated bifidobacteria determined by microfluidic chips and high‐resolution mass spectrometry. Electrophoresis. 2014 Jun;35(11):1742-50.
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