Bioavailability of 6'-Sialyllactose and 3'-Sialyllactose: Dynamic Interplay between Intestinal Absorption and...

Area of Science:

• Human Milk Oligosaccharides Research
• Nutritional Biochemistry
• Pharmacokinetics

Background:

• Sialyllactose (SL) is a key acidic human milk oligosaccharide.
• Understanding the differential pharmacokinetic properties of SL isomers is crucial for their application.

Purpose of the Study:

• To compare the absorption, distribution, metabolism, and excretion (ADME) of 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL).
• To elucidate the potential of 6'-SL in enhancing brain sialic acid (SA) bioavailability.

Main Methods:

• Oral administration of SL isomers in a study model.
• Analysis of SA concentrations in various tissues and fluids (intestine, brain, serum, urine).
• In vitro Caco-2 cell absorption assays and fermentation studies.

Main Results:

• SLs were hydrolyzed to SA in the large intestine.
• 6'-SL group showed higher intestinal and brain SA concentrations.
• 3'-SL group exhibited higher serum and urine conjugated SA levels.
• 3'-SL demonstrated higher energy-dependent absorption in Caco-2 cells compared to 6'-SL.
• SA was the primary metabolite during in vitro fermentation, with 6'-SL showing a lower hydrolysis rate than 3'-SL.

Conclusions:

• Significant differences exist in the ADME profiles of 3'-SL and 6'-SL.
• 6'-SL's slower hydrolysis and absorption, coupled with reduced excretion, suggest potential for increased brain SA bioavailability.
• These findings highlight isomer-specific effects of SLs on SA delivery.