A write- up of associate professor Marion Aw (Paediatric Gastroenterologist)

The milk fat globule membrane (MFGM) contains many bioactive compounds, including gangliosides and sphingolipids, which appear to be involved in establishing and maintaining gut health. Various types of studies indicate that MFGM fractions may exhibit beneficial properties in the gut. Further studies to investigate these properties in infants are needed to fully clarify the mechanisms involved and to fully determine the clinical relevance of these benefits in neonates.

Background: the role of gangliosides in gut health

Diarrhoea in children - Assoc. Prof. Marion Aw, Singapore 2Gangliosides are found in mammalian milk, where they are almost exclusively associated with the MFGM (3-4). The concentrations and composition of gangliosides differ between species, with monosialoganglioside 3 (GM3) being the predominant ganglioside in human milk and disialoganglioside 3 (GD3) being the predominant form of gangliosides in bovine milk.GD3 is the most abundant ganglioside in human colostrum, but the proportion of GM3 increases over time so that it is predominant in more mature human breast milk (3).

Gangliosides have been implicated in gut health of the developing infant. This is thought to occur through the following mechanisms (3); (i) inhibition of the adhesion of toxins, bacteria and viruses to receptors on the surface of gut epithelial cells, (ii) promotion of the growth of Bifidobacteria and Lactobacilli in the digestive tract, and (iii) binding to specific enterotoxigenic Escherichia coli strains, thereby preventing bacterial attachment to mucosa (6-7). Gangliosides may also play a role in intestinal immunity development through lymphocyte activation and differentiation (8).

Role of MFGM in determining gut microflora

Interestingly, ganglioside-supplemented infant formula has been reported to change the intestinal ecology of preterm new-borns, increasing Bifidobacteria numbers and decreasing those of E. coli in the faeces (see figure 1) (3,8)

Figure 1 Bacterial counts in faeces of premature new-born infants fed milk formula (MF) or milk formula supplemented with gangliosides (GMF) (3,8)

Milk fat globules and gut health 1

Adapted from Rueda R. et al (2007)

Role of MFGM in gut development

Studies in animal models indicate that MFGM may play a role in neonatal gut maturation. For example, 7-day rat pups fed milk containing 0.5% sphingomyelin, a component of MFGM, were found to have increased enzymatic and morphological maturation of the intestinecompared with rats fed milk supplemented with 0.5% phosphatidylcholine, or with rats fed control milk. (9)

Role of MFGM in intestinal integrity

Studies in animal models suggest that a diet rich in MFGM exerts a protective effect against gastrointestinal leakiness and injury (2,10-12) A rat study highlighted the involvement of gangliosides in the maintenance of gut integrity by inhibiting the degradation of tight junction proteins during acute inflammation (10). Recombinant milk fat globule-EGF factor 8 (MFG-E8)was shown to play an important role in the maintenance of intestinal epithelial homeostasis and mucosal integrity in the mouse intestinal tract, and it also assisted in the healing of damaged intestinal mucosa in an in vitro model (12) MFG-E8, also known as lactadherin, is a glycoprotein which is abundant in bovine milk fat globules (13).

MFGM and the reduction of incidence of diarrhoea

In a 6-month, randomized, double-blind study, 550 infants received complementary food with the protein source being either the MFGM protein fraction or skim milk proteins (control) (14).  The incidence of diarrhoea(3.84% vs. 4.37%; p<0.05) or bloody diarrhoea (odds ratio 0.54; p=0.025) was reduced in the infants receiving the MFGM protein source compared with the control group. The authors of this study suggested that the use of MFGM-enriched dietary supplements to reduce the incidence of  diarrhoea might be more cost-efficient and sustainable than treatment with antibiotics. Potential explanations for the effect of MFGM on the incidence of diarrhoea could include its direct effect on gut microflora, its contribution to the normal function of the immune system, or as a result of the MFGM components functioning as a decoy for pathogens.

Conclusion

Various types of studies indicate that MFGM fractions may exhibit beneficial properties in the gut. Further studies to investigate these properties in infants are needed to fully clarify the mechanisms involved and to fully determine the clinical relevance of these benefits in neonates.

References

  1. Hernell, O. et al (2016). Clinical Benefits of Milk Fat Globule Membranes for Infants and Children. The Journal of Pediatrics, 2016; 173:S60-S65.
  2. Snow, D.R. et al (2011). Membrane-rich milk fat diet provides protection against gastrointestinal leakiness in mice treated with lipopolysaccharide. Journal of Dairy Science, 2011;94:2201-2212.
  3. Rueda, R. (2007). The role of dietary gangliosides on immunity and the prevention of infection. British Journal of Nutrition, 2007; 98:S68-S73.
  4. Peterson, R. et al (2013). Glycoconjugates in human milk: Protecting infants from disease. Glycobiology 2013;12:1425-1438.
  5. Nakano, T. et al (2000). Acta Paediatr Taiwanica 2000;42:11-17.
  6. Salcedo, J. et al (2013). Food Chem 2013;136:726-734.
  7. Idota T, Kawakami H. Biosci Biotechnol Biochem 1995;59:69-72.
  8. Rueda R, et al. Early Hum Dev 1998;53:S135-S147.
  9. Motouri M, et al. J Pediatr Gastroenterol Nutr 2003;36:241-247.
  10. Park EJ, et al. J Pediatr Gastroenterol Nutr 2010;50:321-328.
  11. Hintze KJ, et al. Biotechnol Biopolym 2011:321-342.
  12. Bu H-F, et al. J Clin Invest 2007;117:3673-3683.
  13. Hettinga, K. et al (2011). The host defense proteome of human and bovine milk. PLoS One 2011;6:e19433.
  14. Zavaleta, N. et al (2011). Efficacy of an MFGM-enriched complementary food in diarrhea, anemia, and micronutrient status in infants. Journal of Pediatric Gastroenterology and Nutrition, 2011;53:561-568.