title: Impact of prebiotics on metabolic and behavioral alterations in a mouse model of metabolic syndrome.
abstract: Mounting evidence shows that the gut microbiota, an important player within the gut-brain communication axis, can affect metabolism, inflammation, brain function and behavior. Interestingly, gut microbiota composition is known to be altered in patients with metabolic syndrome (MetS), who also often display neuropsychiatric symptoms. The use of prebiotics, which beneficially alters the microbiota, may therefore be a promising way to potentially improve physical and mental health in MetS patients. This hypothesis was tested in a mouse model of MetS, namely the obese and type-2 diabetic db/db mice, which display emotional and cognitive alterations associated with changes in gut microbiota composition and hippocampal inflammation compared to their lean db/+ littermates. We assessed the impact of chronic administration (8weeks) of prebiotics (oligofructose) on both metabolic (body weight, food intake, glucose homeostasis) and behavioral (increased anxiety-like behavior and impaired spatial memory) alterations characterizing db/db mice, as well as related neurobiological correlates, with particular attention to neuroinflammatory processes. Prebiotic administration improved excessive food intake and glycemic dysregulations (glucose tolerance and insulin resistance) in db/db mice. This was accompanied by an increase of plasma anti-inflammatory cytokine IL-10 levels and hypothalamic mRNA expression of the anorexigenic cytokine IL-1β, whereas unbalanced mRNA expression of hypothalamic orexigenic (NPY) and anorexigenic (CART, POMC) peptides was unchanged. We also detected signs of improved blood-brain-barrier integrity in the hypothalamus of oligofructose-treated db/db mice (normalized expression of tight junction proteins ZO-1 and occludin). On the contrary, prebiotic administration did not improve behavioral alterations and associated reduction of hippocampal neurogenesis displayed by db/db mice, despite normalization of increased hippocampal IL-6 mRNA expression. Of note, we found a relationship between the effect of treatment on dentate gyrus neurons and spatial memory. These findings may prove valuable for introducing novel approaches to treat some of the comorbidities associated with MetS.
authors.affiliation: INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France.
authors.forename: Lourdes Fernández
authors.initials: LF
authors.lastname: de Cossío
authors.affiliation: INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France.
authors.forename: Célia
authors.initials: C
authors.lastname: Fourrier
authors.affiliation: INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Sauvant
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life Sciences and Biotechnology), Metabolism and Nutrition Research Group, 1200 Brussels, Belgium.
authors.forename: Amandine
authors.initials: A
authors.lastname: Everard
authors.affiliation: INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Capuron
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life Sciences and Biotechnology), Metabolism and Nutrition Research Group, 1200 Brussels, Belgium.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.affiliation: INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Layé
authors.affiliation: INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France. Electronic address: nathalie.castanon@inra.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Castanon
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001644:Bifidobacterium; D001812:Blood-Brain Barrier / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000382:microbiology*; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D056692:Prebiotics / Q000008:administration & dosage*; D065852:Spatial Memory
chemical_list: D056692:Prebiotics
keywords: Anxiety; Cytokines; Gut microbiota; Hippocampus; Hypothalamus; Inflammation; Metabolic syndrome; Prebiotics; Spatial memory; db/db mice