Milk Fat Globule Membranes: Effects on Microbiome, Metabolome, and infections in Infants and Children

Summary

The composition of human milk is optimal to meet the nutritional needs for infant growth and development during the first 4–6 months of life. The milk fat globule (MFG) consists of a core of mainly energy-rich triglycerides enveloped by a unique membrane structure, the milk fat globule membrane (MFGM). MFGM is composed of a phospholipid and cholesterol triple layer with incorporated proteins and glycoproteins. Milk phospholipids, sphingomyelins, and gangliosides are largely located on the MFGM [1]. Several studies reported various health benefits of feeding bovine MFGM to
humans of different age groups, including infants and children. We found 5
double-blind randomized controlled trials exploring the effects of supplementing the diet of infants and children with bovine MFGM concentrates on infections (Table 1) [2, 3]. Two of these (Peru and Sweden) found a protective effect (on bloody diarrhea and otitis media) in infants, and one reported fewer days with fever (5- to 7-year-old Belgian children) (Table 1).

The Swedish study investigated plasma and erythrocyte lipidome and oral, plasma, and fecal metabolome as well as fecal microbiome. There were significant differences in both plasma and erythrocyte membrane lipidomes between the MFGM-supplemented experimental formula (EF) and the group fed standard formula (SF) mostly due to differences in sphingomyelin and phosphatidylcholine concentrations but not at 12 months of age [4].

In 30 randomly selected infants from each group (EF, SF, and a breastfed [BF] reference group), plasma metabolomes were analyzed by NMR. Overall differences between the formula-fed groups (FF) and the BF group were much larger than between EF and SF groups. Interestingly, however, the EF group had higher levels of fatty acid oxidation products than the SF group, which is typical for BF infants. These differences disappeared after the introduction of complementary feeding. Thus, MFGM may have a role in directing infant metabolism [5].


The oral microbiota analyzed by Illumina MiSeq multiplex sequencing exhibited moderate effects on oral microbiota. Species richness did not differ between the EF and SF groups, but a few taxa that were significantly associated with being in either group were identified, e.g., a lower level of Moraxella catarrhalis in the EF group. Of note, M. catarrhalis is one of the major otitis media pathogens, and this finding may thus be associated with a decrease in otitis media seen in the EF group compared
to the SF group [6].

Fecal microbiota analysis was performed by 16S rRNA gene sequencing. While the impact of EF on the fecal microbiome was minor compared to the SF group, the fecal metabolome of EF infants showed a significant reduction in several metabolites, including lactate, succinate, amino acids, and their derivatives, compared to SF infants. Again, the introduction of complementary food with either human milk or infant formula
reduced the distinct BF or FF characteristics of the fecal microbiome and metabolome profiles in infants. The findings support the hypothesis that higher protein levels in infant formula promote a shift towards amino acid fermentation in the gut, and that MFGM may play a role in shaping gut microbial activity and function [7].

In conclusion, studies have shown that feeding infants MFGM reduces the risk of infections and affects the plasma and erythrocyte membrane lipidomes, which might be reflected by improved neurode- velopment. Further, MFGM also modifies the oral microbiome, which may contribute to less risk of otitis media and exerts a minor impact on the fecal microbiome but drives the metabolic phenotype profile towards fatty acid oxidation, which is typical for BF infants but not FF infants.

References
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