Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-d-aspartate receptor subunits and d-serine

Helene M Savignac,Giulia Corona,Henrietta Mills,Li Chen,Jeremy P.E Spencer,George Tzortzis,Philip W.J Burnet

doi:10.1016/j.neuint.2013.10.006

Helene M Savignac, Giulia Corona + Show 5 more

Open Access

https://doi.org/10.1016/j.neuint.2013.10.006

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Abstract

The influence of the gut microbiota on brain chemistry has been convincingly demonstrated in rodents. In the absence of gut bacteria, the central expression of brain derived neurotropic factor, (BDNF), and N-methyl-d-aspartate receptor (NMDAR) subunits are reduced, whereas, oral probiotics increase brain BDNF, and impart significant anxiolytic effects. We tested whether prebiotic compounds, which increase intrinsic enteric microbiota, also affected brain BDNF and NMDARs. In addition, we examined whether plasma from prebiotic treated rats released BDNF from human SH-SY5Y neuroblastoma cells, to provide an initial indication of mechanism of action.Rats were gavaged with fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS) or water for five weeks, prior to measurements of brain BDNF, NMDAR subunits and amino acids associated with glutamate neurotransmission (glutamate, glutamine, and serine and alanine enantiomers). Prebiotics increased hippocampal BDNF and NR1 subunit expression relative to controls. The intake of GOS also increased hippocampal NR2A subunits, and frontal cortex NR1 and d-serine. Prebiotics did not alter glutamate, glutamine, l-serine, l-alanine or d-alanine concentrations in the brain, though GOSfeeding raised plasma d-alanine. Elevated levels of plasma peptide YY (PYY) after GOS intake was observed. Plasma from GOS rats increased the release of BDNF from SH-SY5Y cells, but not in the presence of PYY antisera. The addition of synthetic PYY to SH-SY5Y cell cultures, also elevated BDNF secretion.We conclude that prebiotic-mediated proliferation of gut microbiota in rats, like probiotics, increases brain BDNF expression, possibly through the involvement of gut hormones. The effect of GOS on components of central NMDAR signalling was greater than FOS, and may reflect the proliferative potency of GOS on microbiota. Our data therefore, provide a sound basis to further investigate the utility of prebiotics in the maintenance of brain health and adjunctive treatment of neuropsychiatric disorders.

Highlights

There is compelling evidence for a link between the enteric microbiota and brain function
The numbers of Bifidobacteria in faecal pellets from FOS-fed rats were significantly greater than controls in an ANOVA and post hoc (Tukey HSD) analysis i.e. controls: 2.38 Â 109 ± 0.23 Â 109 vs FOS: 2.98 Â 109 ± 0.22 Â 109, p < 0.05), whereas the numbers of Bifidobacteria from GOS-fed animals were significantly greater than both controls and FOS-fed rats i.e. controls: 2.38 Â 109 ± 0.23 Â 109 vs GOS: 4.28 Â 109 ± 0.43 Â 109, p < 0.01; and FOS: 2.98 Â 109 ± 0.22 Â 109 vs GOS: 4.28 Â 109 ± 0.43 Â 109, p < 0.05
The specific hypotheses tested were, first, that Bifidobacteria proliferation by prebiotics is associated with an increase in brain brain-derived neurotrophic factor (BDNF), as evinced with probiotics; and second, that prebiotic augmentation of commensal microbiota elevates central N-methyl-D-aspartate receptors (NMDARs) subunits, given that these receptors are reduced in germ-free rodents

Summary

Introduction

There is compelling evidence for a link between the enteric microbiota and brain function. The proliferation of the Bifidobacteria and Lactobacilli strains in the large intestine, have anxiolytic and mnemonic effects in both rodents (Li et al, 2009; Bravo et al, 2011) and humans (Messaoudi et al, 2011a,b; Rao et al, 2009; Cryan and Dinan, 2012). The intake of these bacteria as live. Augmenting the growth of intrinsic gut microbiota with prebiotics (nutrients for intestinal bacteria) may afford greater benefits to the brain (Burnet, 2012)

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