3'sialyllactose and 6'sialyllactose enhance performance in endurance- type exercise through metabolic adaptation

Human milk oligosaccharides (HMOs) belong to a group of multifunctional glycans that are abundantly present in human breast milk. While health effects of neutral oligosaccharides have been investigated extensively, a lot remains unknown regarding health effects of acidic oligosaccharides, such as the two sialyllactoses (SLs), 3'sialyllactose (3'SL), and 6'sialyllactose (6'SL). We utilized Caenorhabditis elegans (C. elegans) to investigate the effects of SLs on exercise performance. Using swimming as an endurance -type exercise, we found that SLs decrease exhaustion, signifying an increase in endurance that is strongest for 6'SL. Through an unbiased metabolomics approach, we identified changes in energy metabolism that correlated with endurance performance. Further investigation suggested that these metabolic changes were related to adaptations of muscle mitochondria that facilitated a shift from beta oxidation to glycogenolysis during exercise. We found that the effect of SLs on endurance performance required AMPK-(aak-1/aak-2) and adenosine receptor (ador-1) signaling. We propose a model where SLs alter the metabolic status in the gut, causing a signal from the intestine to the nervous system toward muscle cells, where metabolic adaptation increases exercise performance. Together, our results underline the potential of SLs in exercise-associated health and contribute to our understanding of the molecular processes involved in nutritionally-induced health benefits.

Automated summary

Human milk oligosaccharides (HMOs) are multifunctional glycans abundant in human breast milk. This study investigated the effects of two acidic HMOs, 3'sialyllactose (3'SL) and 6'sialyllactose (6'SL), on exercise performance using Caenorhabditis elegans. The results showed that SLs, especially 6'SL, decreased exhaustion and increased endurance in swimming exercise. Metabolomics analysis revealed changes in energy metabolism, particularly in muscle mitochondria, and the involvement of AMPK and adenosine receptor signaling. SLs were found to alter gut metabolism, leading to improved exercise performance through a signal from the intestine to the nervous system. These findings contribute to our understanding of nutritionally-induced health benefits.