Direct Evidence for the Presence of Human Milk Oligosaccharides in the Circulation of Breastfed Infants

Abstract

BackgroundIt has been hypothesized that human milk oligosaccharides (HMOs) confer systemic health benefits to breastfed infants; however, plausible mechanisms for some effects, such as systemic immunomodulation, require HMOs to access the bloodstream of the developing infant. While small concentrations of HMOs have been detected in the urine of breastfed infants there are no published studies of these oligosaccharides accessing the plasma compartment of breastfed infants. Here we determined the relative fractions of several ingested HMOs in infant urine and plasma. Plasma from formula-fed infants was used as a control.MethodsUsing gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry/tandem mass spectrometry (LC/MS/MS), and high performance liquid chromatography (HPLC), we analyzed the urine and plasma from 17 healthy formula-fed infants and 16 healthy breast-fed infants (and the milk from their mothers).ResultsMultiple HMOs were detected in the urine and plasma of breastfed infants, but not in formula-fed infants. Levels of 2′-fucosyllactose (2′FL), 3FL and lacto-N-neotetraose (LNnT) in both plasma (r = 0.98, p<0.001; r = 0.75, p = 0.002; r = 0.71, p = 0.004) and urine (r = 0.81, p<0.001; r = 0.56, p = 0.026; NS) correlated significantly with concentrations in the corresponding breast milk. The relative fractions of HMOs were low, 0.1% of milk levels for plasma and 4% of milk levels for urine. Within the breastfed cohort, there were significant differences between secretor and nonsecretor groups in levels of several fucosylated HMOs.ConclusionAt least some ingested HMOs are absorbed intact into the circulation and excreted in the urine and their concentrations in these fluids correlate with levels of the corresponding mother's milk. While relative fractions of absorbed HMOs were low, these levels have been shown to have biological effects in vitro, and could explain some of the postulated benefits of human milk.

Galacto-oligosaccharides Protect the Intestinal Barrier by Maintaining the Tight Junction Network and Modulating the Inflammatory Responses after a Challenge with the Mycotoxin Deoxynivalenol in Human Caco-2 Cell Monolayers and B6C3F1 Mice

“…The difference between the results obtained with dual exposure of GOS to the apical and basolateral compartment, which were more pronounced than an application to the apical compartment only, were unexpected because Gnoth et al (38) and Eiwegger et al (39) showed in vitro evidence for a transport of human milk oligosaccharides and prebiotic oligosaccharides, like GOS, across the intestinal epithelial layer. These findings suggest an absorption of orally applied GOS, which was recently supported by the presence of human milk oligosaccharides in the circulation (plasma and urine) of breastfed infants (40). A possible explanation for the different results in the current experiments regarding the route of GOS exposure could be the rather short preincubation time of 24 h, which might not be sufficient to allow an equilibrium between both compartments by means of transcellular transport of GOS.…”

Dietary 2’-Fucosyllactose Enhances Operant Conditioning and Long-Term Potentiation via Gut-Brain Communication through the Vagus Nerve in Rodents

“…On regards to this, it has been reported that a relatively small amount of intact HMOs is absorbed from the intestine into systemic circulation after oral administration. This phenomenon has been described in animal models using neonatal pups [54] and adult rats [55] as well as in breastfed infants [56]. Thus, HMOs present in the bloodstream may, potentially, reach the brain and somehow modulate CNS function.…”

Effects of a human milk oligosaccharide, 2′-fucosyllactose, on hippocampal long-term potentiation and learning capabilities in rodents

“…Despite the fact that 2'-FL has been found in the urine of breastfed babies [18,54,55], which suggests it is absorbed and transported through the bloodstream without modification, there is no published report confirming the presence of 2'-FL in human plasma. Recently, our group detected 2'-FL in the plasma of rats after oral administration [56], suggesting that a mechanism of export from the intestine into the circulation does exist.…”