Abstract
Human milk delivers an array of bioactive components that safeguard infant growth and development and maintain healthy gut microbiota. Milk fat globule membrane (MFGM) is a biologically functional fraction of milk increasingly linked to beneficial outcomes in infants through protection from pathogens, modulation of the immune system and improved neurodevelopment. In the present study, we characterized the fecal microbiome and metabolome of infants fed a bovine MFGM supplemented experimental formula (EF) and compared to infants fed standard formula (SF) and a breast-fed reference group. The impact of MFGM on the fecal microbiome was moderate; however, the fecal metabolome of EF-fed infants showed a significant reduction of several metabolites including lactate, succinate, amino acids and their derivatives from that of infants fed SF. Introduction of weaning food with either human milk or infant formula reduces the distinct characteristics of breast-fed- or formula-fed- like infant fecal microbiome and metabolome profiles. Our findings support the hypothesis that higher levels of protein in infant formula and the lack of human milk oligosaccharides promote a shift toward amino acid fermentation in the gut. MFGM may play a role in shaping gut microbial activity and function.
Highlights
Breastfeeding influences the development of the gut microbiota according to the degree of exclusivity[1,2]
To provide a mechanistic explanation regarding the influence of milk fat globule membrane (MFGM) on gut microbiota, we evaluated the fecal microbiome and metabolome of a subgroup of 90 infants who participated in a prospective, double-blind, randomized controlled study[28,29], where FF infants were randomly assigned to receive a standard infant formula (SF) or a bovine MFGM isolate-supplemented, low-energy, low-protein experimental formula (EF) from ~2 until 6 months of age
Out of a total of 240 infants who participated in a clinical trial concerning the outcomes of feeding a formula supplemented with a bovine MFGM isolate, which initially consisted of BF, n = 80; standard formula (SF)-fed, n = 80, and EF-fed, n = 80 (ClinicalTrials.gov identifier: NCT00624689), following exclusions[28,29] a subset of 90 infants (15 males and 15 females from each treatment group) were randomly selected for fecal microbiome and metabolome analysis at 2, 4, 6, and 12 months. 96.2%, 96.5% and 82.1% of infants in the BF, SF, and EF group respectively were born vaginally
Summary
Breastfeeding influences the development of the gut microbiota according to the degree of exclusivity[1,2]. Circulating lysine and threonine, that we previously found to be higher in FF infants[13], are considered metabolites with a gut microbial origin[18,19,20], as modification of intestinal microbiota via prebiotic supplementation has been shown to reduce free amino acids in cecum, colon, serum and liver of adult mice[21], and to slightly lower the blood urea level of infants[22]. These studies support the importance of exploring gut microbiota as contributing factors to infant metabolism. These studies led to the hypothesis that MFGM may act as a substrate that selectively promotes growth of healthy infant gut microbiota, and that supplementing an MFGM concentrate may alter gut microbial composition and by-products to a profile that is more similar to an exclusively BF reference group
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