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

Abstract

This study builds on a previous study by this group in which 6-11-month-old Peruvian infants who were fed bovine milk fat globule membrane (MFGM) containing complementary food had significantly fewer episodes of infection-related bloody diarrhea relative to those consuming a control food (skim milk powder). Micronutrient deficiencies including zinc deficiency were prevalent in this study population. To understand the mechanism behind the health benefits of consuming MFGM, the serum metabolome and cytokine levels, as markers for systemic immune responses, were evaluated using ¹H nuclear magnetic resonance-based metabolomics and a multiplex system, respectively. Combined with data on micronutrient status and anthropometry, a comparative analysis was performed. Supplementation with MFGM tended to improve micronutrient status, energy metabolism, and growth reflected as increased levels of circulating amino acids and weight gain, particularly in female infants compared to controls. Decreased levels of the microbial choline metabolite trimethylamine-N-oxide in the MFGM-supplemented group (both male and female infants) suggest a functional perturbation in the intestinal microbiota. A cytokine shift toward a less T helper type 1 response was observed in those receiving the MFGM supplement, which was mainly attributed to decreases in interleukin-2 levels. Our findings suggest that consumption of MFGM with complementary food may reverse the metabolic abnormalities found in marginally nourished infants, thereby improving metabolic regulation, which may lead to enhanced immunity.

Keywords: Developing world; Metabolomics.

Fig. 1

MFGM supplementation with complementary food for 6 months significantly alters host-microbial choline metabolism. Data are presented as median (solid line) ± interquartile range (IQR) in the box plot, and whiskers extend to the 1.5 IQR values. Group differences with approaching significance (0.05 < ^#P < 0.1) or significance (0.1 < *P < 0.05, **P < 0.01) are noted. TMA trimethylamine, TMAO trimethylamine-N-oxide, FMO flavin-containing monooxygenase

Fig. 2

Serum cytokine levels of infants in the MFGM (orange) and the control (blue) groups. a Fold change of each cytokine from baseline assessment was calculated as FC (post-/pre) value (expressed as median ± interquartile range). IL-2 concentrations were significantly decreased in the MFGM supplemented group. b Th1/Th2 ratio (defined as the ratio of Th1 (IFN-γ, and IL-2) to Th2 cytokines (IL-4, IL-5, and IL-10)) was significantly different between groups after supplementation (*P < 0.05; Mann-Whitney) (expressed as median with 95% Cl)

Fig. 3

a Serum vitamin B12 was significantly higher in the MFGM group (orange filled circle) compared with the control group (blue empty circle) after 6-months of micronutrient supplementation. Data are presented as median (solid line) ± interquartile range (IQR). b Spearman rank correlation between the serum metabolites, cytokines, and micronutrient concentration post-intervention. Data showing at least moderate correlation (|ρ| > 0.4) were selected. The intensity of color represents the magnitude of the correlation, and the color indicates either positive (red color; 0 < ρ < 1), or negative correlations (blue color; −0.5 < ρ < 0). ρ = correlation coefficient

Fig. 4

Male (n = 28 (MFGM); 24 (control)) and female infants (n = 18 (MFGM); 21 (control)) showed different responses to MFGM supplementation. a Heatmap showing the log₂FC of serum metabolites associated with amino acid metabolism. Color code indicates negative (red) to positive (green) changes. Changes in the serum levels of b Zinc (μg/ml), and c ferritin (μg/ml); and changes in (d–e) anthropometric data (weight expressed as kg) calculated by subtracting the initial values from the final values of measurements are shown with identified sex differences (0.05 < ^#P < 0.1; *P < 0.05; **P < 0.01). Data are presented as median (solid line) ± interquartile range (IQR) in the box plot, and whiskers extends to the 1.5 IQR values. EAA essential amino acid, NEAA non-essential amino acid, AA amino acid