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

PLoS One. 2016 Nov 16;11(11):e0166070. doi: 10.1371/journal.pone.0166070. eCollection 2016.


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 gut-brain 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.

MeSH terms

  • Administration, Oral
  • Animals
  • Brain / drug effects
  • Brain / physiology*
  • Conditioning, Operant / drug effects*
  • Diet*
  • Digestive System / drug effects*
  • Fucose / administration & dosage
  • Fucose / pharmacology
  • Long-Term Potentiation / drug effects*
  • Male
  • Rats, Sprague-Dawley
  • Trisaccharides / administration & dosage
  • Trisaccharides / pharmacology*
  • Vagotomy
  • Vagus Nerve / drug effects
  • Vagus Nerve / physiology*


  • Trisaccharides
  • Fucose
  • 2'-fucosyllactose

Grants and funding

The study has been exclusively funded by Abbott Nutrition. The funder provided support in the form of salaries for authors [EV, AB, MR, MLJ, RB, RR] as well as budget for expenses associated with experimental work. The funder did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.