Cited by 98Infant Nutrition and HealthMicrobial Metabolites in Food BiotechnologyProtein Hydrolysis and Bioactive Peptides

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

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Vazquez, Enrique, Barranco, Alejandro, Ramirez, Maria, Gruart, Agnes, Delgado-Garcia, Jose M., Jimenez, Maria L., Buck, Rachael, Rueda, Ricardo·2016·PLOS ONE

Abstract

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.

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  • Subdiaphragmatic vagal deafferentation highlights the involvement of vagal afferents in anxiety-like and fear-related behavior.

    “In addition, subdiaphragmatic vagal deafferentation (Vazquez et al., 2016) a method that eliminates abdominal vagal afferents, but keeps most efferents intact (Norgren and Smith, 1994) highlights the involvement of vagal afferents in anxiety-like (elevated plus maze, open-field test, food neophobia) and fear-related behavior (auditory-cued fear conditioning) (Klarer et al.,”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Vazquez et al., 2016

    The Vazquez citation identifies the surgical method, not the later claim about anxiety-like and fear-related behavior. In Material and Methods (page unavailable), Vazquez et al. describe bilateral subdiaphragmatic vagotomy that transects the vagal trunks and branches, rather than selective vagal deafferentation. (LLM, conf=0.86)

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  • Vagotomy inhibits the effects of the prebiotic 2'-Fucosyllactose in associative learning paradigms and hippocampal LTP.

    “Moreover, vagotomy inhibited the effects of the prebiotic 2'-Fucosyllactose in associative learning related paradigms and hippocampal LTP (Vazquez et al., 2016).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Vazquez et al., 2016

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Research works printed but not linked: 55

  1. S Wu, 2011, Annotation and structural analysis of sialylated human milk oligosaccharides, J Proteome Res, 10, 856, 10.1021/pr101006u · DOI
  2. S Wu, 2010, Development of an annotated library of neutral human milk oligosaccharides, J Proteome Res, 9, 4138, 10.1021/pr100362f · DOI
  3. RM Erney, 2000, Variability of human milk neutral oligosaccharides in a diverse population, J Pediatr Gastroenterol Nutr, 30, 181, 10.1097/00005176-200002000-00016 · DOI
  4. N Tao, 2008, Bovine milk glycome, J Dairy Sci, 91, 3768, 10.3168/jds.2008-1305 · DOI
  5. T Urashima, 2013, Recent advances in studies on milk oligosaccharides of cows and other domestic farm animals, Biosci Biotechnol Biochem, 77, 455, 10.1271/bbb.120810 · DOI
  6. L Schack-Nielsen, 2007, Advances in our understanding of the biology of human milk and its effects on the offspring, J Nutr, 137, 503S, 10.1093/jn/137.2.503S · DOI
  7. A Walker, 2010, Breast milk as the gold standard for protective nutrients, J Pediatr, 156, S3, 10.1016/j.jpeds.2009.11.021 · DOI
  8. MS Kramer, 2008, Breastfeeding and child cognitive development: new evidence from a large randomized trial, Arch Gen Psychiatry, 65, 578, 10.1001/archpsyc.65.5.578 · DOI · Paper page
  9. JW Gurd, 1979, Molecular and biosynthetic heterogeneity of fucosyl glycoproteins associated with rat brain synaptic functions, Biochim Biophys Acta, 555, 221, 10.1016/0005-2736(79)90162-7 · DOI
  10. HE Murrey, 2009, Identification of the plasticity-relevant fucose-alpha(1–2)-galactose proteome from the mouse olfactory bulb, Biochemistry, 48, 7261, 10.1021/bi900640x · DOI
  11. R Jork, 1986, Impairment of glycoprotein fucosylation in rat hippocampus and the consequences on memory formation, Pharmacol Biochem Behav, 25, 1137, 10.1016/0091-3057(86)90100-0 · DOI
  12. R Sukumar, 1980, Increased incorporation of [3H]fucose into chick brain glycoproteins following training on a passive avoidance task, J Neurochem, 34, 1000, 10.1111/j.1471-4159.1980.tb09677.x · DOI
  13. SF Cooke, 2006, Plasticity in the human central nervous system, Brain, 129, 1659, 10.1093/brain/awl082 · DOI
  14. A Gruart, 2006, Involvement of the CA3-CA1 synapse in the acquisition of associative learning in behaving mice, J Neurosci, 26, 1077, 10.1523/JNEUROSCI.2834-05.2006 · DOI
  15. E Oliveros, 2016, Oral supplementation of 2'-fucosyllactose during lactation improves memory and learning in rats, J Nutr Biochem, 31, 20, 10.1016/j.jnutbio.2015.12.014 · DOI
  16. E Vazquez, 2015, Effects of a human milk oligosaccharide, 2'-fucosyllactose, on hippocampal long-term potentiation and learning capabilities in rodents, J Nutr Biochem, 26, 455, 10.1016/j.jnutbio.2014.11.016 · DOI
  17. H Matthies, 1996, Fucose and fucosyllactose enhance in-vitro hippocampal long-term potentiation, Brain Res, 725, 276, 10.1016/0006-8993(96)00406-4 · DOI
  18. M Carabotti, 2015, The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems, Ann Gastroenterol, 28, 203
  19. P Keightley, 2015, Gut feelings 1. Mind, mood and gut in irritable bowel syndrome: approaches to psychiatric care, Australas Psychiatry, 23, 403, 10.1177/1039856215590033 · DOI
  20. PC Keightley, 2015, Pathways in gut-brain communication: evidence for distinct gut-to-brain and brain-to-gut syndromes, Aust N Z J Psychiatry, 49, 207, 10.1177/0004867415569801 · DOI
  21. Y Zuo, 2007, Vagus nerve stimulation potentiates hippocampal LTP in freely-moving rats, Physiol Behav, 90, 583, 10.1016/j.physbeh.2006.11.009 · DOI
  22. J Bienenstock, 2013, Fucosylated but not sialylated milk oligosaccharides diminish colon motor contractions, PLoS One, 8, e76236, 10.1371/journal.pone.0076236 · DOI
  23. M Zatz, 1971, Rapid transport of fucosyl glycoproteins to nerve endings in mouse brain, J Neurochem, 18, 1125, 10.1111/j.1471-4159.1971.tb12041.x · DOI
  24. PG Reeves, 1993, AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet, J Nutr, 123, 1939, 10.1093/jn/123.11.1939 · DOI
  25. JA Bravo, 2011, Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve, Proc Natl Acad Sci U S A, 108, 16050, 10.1073/pnas.1102999108 · DOI · Paper page
  26. I Gureviciene, 2004, Normal induction but accelerated decay of LTP in APP + PS1 transgenic mice, Neurobiol Dis, 15, 188, 10.1016/j.nbd.2003.11.011 · DOI
  27. TV Bliss, 1973, Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path, J Physiol, 232, 357, 10.1113/jphysiol.1973.sp010274 · DOI
  28. R Sanchez-Campusano, 2011, Timing and causality in the generation of learned eyelid responses, Front Integr Neurosci, 5, 39, 10.3389/fnint.2011.00039 · DOI
  29. L Bode, 2012, Human milk oligosaccharides: every baby needs a sugar mama, Glycobiology, 22, 1147, 10.1093/glycob/cws074 · DOI · Paper page
  30. E Castanys-Munoz, 2013, 2'-fucosyllactose: an abundant, genetically determined soluble glycan present in human milk, Nutr Rev, 71, 773, 10.1111/nure.12079 · DOI
  31. MP Sherman, 2015, Gut microbiota, the immune system, and diet influence the neonatal gut-brain axis, Pediatr Res, 77, 127, 10.1038/pr.2014.161 · DOI
  32. M Krug, 1994, Fucose and fucose-containing sugar epitopes enhance hippocampal long-term potentiation in the freely moving rat, Brain Res, 643, 130, 10.1016/0006-8993(94)90018-3 · DOI
  33. H Matthies, 2000, Enhancement of glutamate release by L-fucose changes effects of glutamate receptor antagonists on long-term potentiation in the rat hippocampus, Learn Mem, 7, 227, 10.1101/lm.7.4.227 · DOI
  34. H Matthies Jr., 1999, Glycosylation of proteins during a critical time window is necessary for the maintenance of long-term potentiation in the hippocampal CA1 region, Neuroscience, 91, 175, 10.1016/S0306-4522(98)00628-9 · DOI
  35. HE Murrey, 2006, Protein fucosylation regulates synapsin Ia/Ib expression and neuronal morphology in primary hippocampal neurons, Proc Natl Acad Sci U S A, 103, 21, 10.1073/pnas.0503381102 · DOI
  36. JM Pickard, 2015, Intestinal fucose as a mediator of host-microbe symbiosis, J Immunol, 194, 5588, 10.4049/jimmunol.1500395 · DOI
  37. JM Pickard, 2014, Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness, Nature, 514, 638, 10.1038/nature13823 · DOI
  38. S Udit, 2013, Molecular anatomy of the gut-brain axis revealed with transgenic technologies: implications in metabolic research, Front Neurosci, 7, 134, 10.3389/fnins.2013.00134 · DOI
  39. J Bienenstock, 2015, Microbiota and the gut-brain axis, Nutr Rev, 73, 28, 10.1093/nutrit/nuv019 · DOI · Paper page
  40. CH Knowles, 2013, New perspectives in the diagnosis and management of enteric neuropathies, Nat Rev Gastroenterol Hepatol, 10, 206, 10.1038/nrgastro.2013.18 · DOI
  41. G Matteoli, 2013, The vagal innervation of the gut and immune homeostasis, Gut, 62, 1214, 10.1136/gutjnl-2012-302550 · DOI · Paper page
  42. JB German, 2008, Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria, Nestle Nutr Workshop Ser Pediatr Program, 62, 205, 10.1159/000146322 · DOI
  43. L Bode, 2015, The functional biology of human milk oligosaccharides, Early Hum Dev
  44. F De Vadder, 2014, Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits, Cell, 156, 84, 10.1016/j.cell.2013.12.016 · DOI · Paper page
  45. FA Schroeder, 2007, Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse, Biol Psychiatry, 62, 55, 10.1016/j.biopsych.2006.06.036 · DOI · Paper page
  46. E Jantscher-Krenn, 2012, Human milk oligosaccharides and their potential benefits for the breast-fed neonate, Minerva Pediatr, 64, 83
  47. E Jantscher-Krenn, 2012, The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats, Gut, 61, 1417, 10.1136/gutjnl-2011-301404 · DOI
  48. KR Sherrill, 2013, Hippocampus and retrosplenial cortex combine path integration signals for successful navigation, J Neurosci, 33, 19304, 10.1523/JNEUROSCI.1825-13.2013 · DOI · Paper page
  49. JH Peters, 2013, Withdrawal and restoration of central vagal afferents within the dorsal vagal complex following subdiaphragmatic vagotomy, J Comp Neurol, 521, 3584, 10.1002/cne.23374 · DOI · Paper page
  50. ZR Gallaher, 2012, Changes in microglial activation within the hindbrain, nodose ganglia, and the spinal cord following subdiaphragmatic vagotomy, Neurosci Lett, 513, 31, 10.1016/j.neulet.2012.01.079 · DOI
  51. E Jantscher-Krenn, 2013, Human milk oligosaccharides are differentially metabolised in neonatal rats, Br J Nutr, 110, 640, 10.1017/S0007114512005727 · DOI
  52. A Santos-Fandila, 2013, Ultra high performance liquid chromatography-tandem mass spectrometry method for the determination of soluble milk glycans in rat serum, Talanta, 118, 137, 10.1016/j.talanta.2013.10.013 · DOI
  53. KC Goehring, 2014, Direct evidence for the presence of human milk oligosaccharides in the circulation of breastfed infants, PLoS One, e101692, 10.1371/journal.pone.0101692 · DOI
  54. S Rudloff, 2006, Incorporation of orally applied (13)C-galactose into milk lactose and oligosaccharides, Glycobiology, 16, 477, 10.1093/glycob/cwj092 · DOI
  55. S Rudloff, 2012, Urinary excretion of in vivo (1)(3)C-labelled milk oligosaccharides in breastfed infants, Br J Nutr, 107, 957, 10.1017/S0007114511004016 · DOI

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Metadata

Authors
Vazquez, E., Barranco, A., Ramirez, M., Gruart, A., Delgado-Garcia, J. M., Jimenez, M. L., Buck, R., & Rueda, R.
Affiliations
  • Universidad Pablo de Olavide (ES)
  • Abbott Nutrition (United States) (US)
Venue
PLOS ONE
Published
2016-11-16
Volume
11
Issue
11
Pages
e0166070
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2552391811
Cited by
98
References
2
Citations by year
2026: 11 · 2025: 14 · 2024: 14 · 2023: 12 · 2022: 5 · 2021: 13 · 2020: 15 · 2019: 8 · 2018: 5 · 2017: 1
FWCI
4.16
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Abbott Nutrition
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
  • Health Sciences › Nursing › Nutrition and Dietetics › Microbial Metabolites in Food Biotechnology
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Protein Hydrolysis and Bioactive Peptides
Keywords
2'-fucosyllactose, human milk oligosaccharides, gut-brain axis, vagus nerve, long-term potentiation, hippocampus, operant conditioning, associative learning, memory, vagotomy, L-fucose, dietary oligosaccharides, cognitive function
MeSH terms
Administration, Oral, Animals, Brain, Conditioning, Operant, Diet, Digestive System, Fucose, Male, Trisaccharides, Vagotomy, Vagus Nerve, Rats, Sprague-Dawley, Long-Term Potentiation

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