title: Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-β levels in male mice.
abstract: The manipulation of the enteric microbiota with specific prebiotics and probiotics, has been shown to reduce the host's inflammatory response, alter brain chemistry, and modulate anxiety behaviour in both rodents and humans. However, the neuro-immune and behavioural effects of prebiotics on sickness behaviour have not been explored. Here, adult male CD1 mice were fed with a specific mix of non-digestible galacto-oligosaccharides (Bimuno®, BGOS) for 3 weeks, before receiving a single injection of lipopolysaccharide (LPS), which induces sickness behaviour and anxiety. Locomotor and marble burying activities were assessed 4h after LPS injection, and after 24h, anxiety in the light-dark box was assessed. Cytokine expression, and key components of the serotonergic (5-Hydroxytryptamine, 5-HT) and glutamatergic system were evaluated in the frontal cortex to determine the impact of BGOS administration at a molecular level. BGOS-fed mice were less anxious in the light-dark box compared to controls 24h after the LPS injection. Elevated cortical IL-1β concentrations in control mice 28 h after LPS were not observed in BGOS-fed animals. This significant BGOS×LPS interaction was also observed for 5HT2A receptors, but not for 5HT1A receptors, 5HT, 5HIAA, NMDA receptor subunits, or other cytokines. The intake of BGOS did not influence LPS-mediated reductions in marble burying behaviour, and its effect on locomotor activity was equivocal. Together, our data show that the prebiotic BGOS has an anxiolytic effect, which may be related to the modulation of cortical IL-1β and 5-HT2A receptor expression. Our data suggest a potential role for prebiotics in the treatment of neuropsychiatric disorders where anxiety and neuroinflammation are prominent clinical features.
authors.affiliation: Clasado Research Services Ltd, Reading RG6 6BZ, UK.
authors.forename: Helene M
authors.initials: HM
authors.lastname: Savignac
authors.affiliation: Department of Pharmacology, University of Oxford, Oxford OX1, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Couch
authors.affiliation: CR-UK/MRC Oxford Institute for Radiation Oncology, University of Oxford, OX3 7DQ, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Stratford
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford OX1, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Bannerman
authors.affiliation: Clasado Research Services Ltd, Reading RG6 6BZ, UK.
authors.forename: George
authors.initials: G
authors.lastname: Tzortzis
authors.affiliation: Department of Pharmacology, University of Oxford, Oxford OX1, UK.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Anthony
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK. Electronic address: phil.burnet@psych.ox.ac.uk.
authors.forename: Philip W J
authors.initials: PWJ
authors.lastname: Burnet
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000378:metabolism; D000069196:Gastrointestinal Microbiome; D006624:Hippocampus / Q000378:metabolism; D055809:Illness Behavior / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced / Q000178:diet therapy / Q000523:psychology; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D056692:Prebiotics / Q000008:administration & dosage*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D056692:Prebiotics; D044402:Receptor, Serotonin, 5-HT2A; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin
keywords: 5-HT2A receptor; BGOS; Behaviour; Cytokines; Frontal cortex; Inflammation; Microbiota; NMDA receptor