Fucose as a Cleavage Product of 2’Fucosyllactose Does Not Cross the Blood‐Brain Barrier in Mice

Abstract

Scope To further examine the role of the human milk oligosaccharide 2’fucosyllactose (2´FL) and fucose (Fuc) in cognition. Using 13C‐labeled 2’FL,thestudy previously showed in mice that 13C‐enrichment of the brain is not caused by 13C1‐2´FL itself, but rather by microbial metabolites. Here, the study applies 13C1‐Fuc in the same mouse model to investigate its uptake into the brain. Methods and Results Mice received 13C1‐Fuc via oral gavage (2 mmol 13C1‐Fuc/kg‐1 body weight) or intravenously (0.4 mmol/kg‐1 body weight). 13C‐enrichment is measured in organs, including various brain regions, biological fluids and excrements. By EA‐IRMS, the study observes an early rise of 13C‐enrichment in plasma, 30 min after oral dosing. However, 13C‐enrichment in the brain does not occur until 3‐5 h post‐dosing, when the 13C‐Fuc bolus has already reached the lower gut. Therefore, the researcher assume that 13C‐Fuc is absorbed in the upper small intestine but cannot cross the blood‐brain barrier which is also observed after intravenous application of 13C1‐Fuc. Conclusions Late 13C‐enrichment in the rodent brain may be derived from 13C1‐Fuc metabolites derived from bacterial fermentation. The precise role that Fuc or 2´FL metabolites might play in gut‐brain communication needs to be investigated in further studies.

Recent Progress in Human Milk Oligosaccharides and Its Antiviral Efficacy

“…Of noted, this may attribute to the existence of gut microbiota, as the germ-free adult mice dose not detect cleavage products of 2′-FL in brain. 66 Emerging study clearly demonstrates that either 2′-FL or 6′-SL can enhance the integrity of BBB, but only HMO metabolites can traverse the BBB, as no intact HMOs were detected in the brain of mice by nuclear magnetic resonance (NMR). 67…”

“…A clinical trial indicated that 2′-FL downregulated IL-1rα, IL-1α, IL-1β, IL-6, and TNF-α in children aged four months . Recently, Rudloff et al illustrated that 2′-FL does not penetrate into brain via BBB in adult mice, but the degradative products of 2′-FL could reach and adjust the function of the brain. Of noted, this may attribute to the existence of gut microbiota, as the germ-free adult mice dose not detect cleavage products of 2′-FL in brain .…”

“…Recently, Rudloff et al illustrated that 2′-FL does not penetrate into brain via BBB in adult mice, but the degradative products of 2′-FL could reach and adjust the function of the brain. Of noted, this may attribute to the existence of gut microbiota, as the germ-free adult mice dose not detect cleavage products of 2′-FL in brain . Emerging study clearly demonstrates that either 2′-FL or 6′-SL can enhance the integrity of BBB, but only HMO metabolites can traverse the BBB, as no intact HMOs were detected in the brain of mice by nuclear magnetic resonance (NMR) …”

Biology of human milk oligosaccharides: From basic science to clinical evidence

“…The long lasting and improved learning and memory outcomes with 2'‐FL feeding were related to effects on hippocampal memory related gene expression and long‐term potentiation. In additional studies, the effect of 2'‐FL was shown to be mediated via the vagus nerve 188 and not by direct uptake of 2'‐FL or derived fucose into the brain 189,190 . Rather, for any uptake, microbial cleavage of 2'‐FL is necessary.…”

“…In additional studies, the effect of 2'‐FL was shown to be mediated via the vagus nerve 188 and not by direct uptake of 2'‐FL or derived fucose into the brain. 189 , 190 Rather, for any uptake, microbial cleavage of 2'‐FL is necessary. There are relatively few data in humans but, in one study of breastfed infants, greater 2'‐FL intake at 1 month of age predicted better infant cognitive development at 24 months of age.…”