Milk sugars beyond lactose : metabolic fate of neutral milk oligosaccharides in infants

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2015

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DOI:
http://dx.doi.org/10.22029/jlupub-16668

Abstract

Free oligosaccharides in human milk (HMO) are complex carbohydrates structurally based on lactose and present at concentrations of 5-20 g/L. They are considered to be resistant to digestion in the breastfed infant s stomach and small intestine, and to serve as energy source selectively for beneficial microbiota in the bowel. Apart from this prebiotic effect, HMO have been found to exert various biological activities in numerous in vitro studies, that indicate not only local functionality in the gut, but also, e.g. immunomodulatory or anti-infective, effects within the body. However, a direct link between structure and function in vivo has not yet been provided. This, in turn, is due to the enormous structural diversity of HMO: More than 150 different structures have been characterized to date. In this work, the metabolic pathways and excretion profiles of HMO were investigated in vivo to extend our knowledge on the sites of HMO utilization or modification and thereby to provide hints on the structure-function relationship of HMO in the infant. Therefore, a platform based on solid phase extraction and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for a high throughput-profiling of oligosaccharides from human milk, infants urine and feces was established, complemented by isomer separation via liquid chromatography. It was used to follow the time course and possible metabolites of 13C-enriched and non-enriched oligosaccharides in milk and infant urine from ten mother-infant pairs during 36 hours after the application of 13C-galactose to the mothers. Intestinal absorption and subsequent renal excretion of intact structures, in particular (fucosylated) hexaoses, could be deduced for all infants. However, in some infants, excretion was delayed, pointing at a longer gut passage or systemic circulation of those certain structures. Moreover, structure-specific modifications and utilization in the upper parts of the gut, where absorption is thought to take place, were hypothesized. The overall oligosaccharide profiles in the feces of breastfed infants could be categorized into three groups, i.e. i) high diversity with many HMO-like structures, ii) only one or a few oligosaccharides with rather low signal intensity, and iii) no HMO. The patterns showed some association with the infants age. However, further research is needed to investigate the underlying causes, e.g. gut maturity or stool frequency. Novel metabolites were identified in both, infant urine and feces. They could be characterized as acetylated HMO or HMO degradation/modification products, generated by the infants or by their gut microbiota, such as secretor- or Lewis-specific HMO in the feces/urine of infants fed nonsecretor or Lewis-negative milk. Lacto-N-tetraose as a major oligosaccharide in milk was significantly reduced especially in fecal samples. Moreover, the secretor-specific structure lacto-N-fucopentaose I, which is highly abundant in secretor milk, was not detected in the urine of the infants fed Lewis b secretor milk, which indicates a selective utilization of this specific structure.

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