Identification of Milk and Cheese Intake Biomarkers in Healthy Adults Reveals High Interindividual Variability of Lewis System–Related Oligosaccharides

https://doi.org/10.1093/jn/nxaa029Get rights and content
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ABSTRACT

Background:

The use of biomarkers of food intake (BFIs) in blood and urine has shown great promise for assessing dietary intake and complementing traditional dietary assessment tools whose use is prone to misreporting.

Objective:

Untargeted LC-MS metabolomics was applied to identify candidate BFIs for assessing the intake of milk and cheese and to explore the metabolic response to the ingestion of these foods.

Methods:

A randomized controlled crossover study was conducted in healthy adults [5 women, 6 men; age: 23.6 ± 5.0 y; BMI (kg/m2): 22.1 ± 1.7]. After a single isocaloric intake of milk (600 mL), cheese (100 g), or soy-based drink (600 mL), serum and urine samples were collected postprandially up to 6 h and after fasting after 24 h. Untargeted metabolomics was conducted using LC-MS. Discriminant metabolites were selected in serum by multivariate statistical analysis, and their mass distribution and postprandial kinetics were compared.

Results:

Serum metabolites discriminant for cheese intake had a significantly lower mass distribution than metabolites characterizing milk intake (P = 4.1 × 10-4). Candidate BFIs for milk or cheese included saccharides, a hydroxy acid, amino acids, amino acid derivatives, and dipeptides. Two serum oligosaccharides, blood group H disaccharide (BGH) and Lewis A trisaccharide (LeA), specifically reflected milk intake but with high interindividual variability. The 2 oligosaccharides showed related but opposing trends: subjects showing an increase in either oligosaccharide did not show any increase in the other oligosaccharide. This result was confirmed in urine.

Conclusions:

New candidate BFIs for milk or cheese could be identified in healthy adults, most of which were related to protein metabolism. The increase in serum of LeA and BGH after cow-milk intake in adults calls for further investigations considering the beneficial health effects on newborns of such oligosaccharides in maternal milk. The trial is registered at clinicaltrials.gov as NCT02705560.

Keywords:

biomarker
dairy
cheese
milk
soy
postprandial
metabolomics
serum metabolome
Lewis antigen

Abbreviations used:

BFI
biomarker of food intake
BGH
blood group H disaccharide
CV-ANOVA
ANOVA of the cross-validated residuals
FoodBAll
Food Biomarkers Alliance
FP
phenylalanyl-proline
FUT
fucosyltransferase
iAUC
incremental AUC
ILA
indole-3-lactic acid
LeA
Lewis A trisaccharide
nparLD
nonparametric analysis of longitudinal data
OPLS-DA
orthogonal projections to latent structures discriminant analysis
PLS-DA
partial least-square discriminant analysis
VIP
variable importance in projection for the predictive component
VT
valyl-threonine

Cited by (0)

The study was funded by the Swiss National Science Foundation (40HD40_160618) in the frame of the national research program “Healthy Nutrition and Sustainable Food Protection” (NRP69) and the European Healthy Diet for a Healthy Life Joint Programming Initiative “The Food Biomarkers Alliance” (FoodBAll).

Author disclosures: The authors report no conflicts of interest.