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

2'-fucosyllactose (2'-FL) is an abundant human milk oligosaccharide (HMO) in human milk with diverse biological effects. We recently reported ingested 2'-FL stimulates central nervous system (CNS) function, such as hippocampal long term potentiation (LTP) and learning and memory in rats. Conceivably the effect of 2'-FL on CNS function may be via the gutbrain axis (GBA), specifically the vagus nerve, and L-fucose (Fuc) may play a role. This study had two aims: (1) determine if the effect of ingested 2'-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2) confirm if oral 2'-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy. Results showed that 2'-FL but not Fuc enhanced LTP, and vagotomy inhibited the effects of oral 2'-FL on LTP and associative learning related paradigms. Taken together, the data show that dietary 2'-FL but not its Fuc moiety affects cognitive domains and improves learning and memory in rats. This effect is dependent on vagus nerve integrity, suggesting GBA plays a role in 2'-FL-mediated cognitive benefits.