title: Microbiota and host determinants of behavioural phenotype in maternally separated mice.
abstract: Early-life stress is a determinant of vulnerability to a variety of disorders that include dysfunction of the brain and gut. Here we exploit a model of early-life stress, maternal separation (MS) in mice, to investigate the role of the intestinal microbiota in the development of impaired gut function and altered behaviour later in life. Using germ-free and specific pathogen-free mice, we demonstrate that MS alters the hypothalamic-pituitary-adrenal axis and colonic cholinergic neural regulation in a microbiota-independent fashion. However, microbiota is required for the induction of anxiety-like behaviour and behavioural despair. Colonization of adult germ-free MS and control mice with the same microbiota produces distinct microbial profiles, which are associated with altered behaviour in MS, but not in control mice. These results indicate that MS-induced changes in host physiology lead to intestinal dysbiosis, which is a critical determinant of the abnormal behaviour that characterizes this model of early-life stress.
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, HSC 4W8, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: G
authors.initials: G
authors.lastname: De Palma
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, HSC 4W8, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: P
authors.initials: P
authors.lastname: Blennerhassett
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, HSC 4W8, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, HSC 4W8, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: Y
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, HSC 4W8, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: A J
authors.initials: AJ
authors.lastname: Park
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, HSC 4W8, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: W
authors.initials: W
authors.lastname: Green
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, HSC 4W8, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: E
authors.initials: E
authors.lastname: Denou
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, HSC 4W8, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: M A
authors.initials: MA
authors.lastname: Silva
authors.affiliation: Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia 46980, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Santacruz
authors.affiliation: Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia 46980, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Sanz
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, HSC 4W8, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: M G
authors.initials: MG
authors.lastname: Surette
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, HSC 4W8, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: E F
authors.initials: EF
authors.lastname: Verdu
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, HSC 4W8, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: S M
authors.initials: SM
authors.lastname: Collins
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, HSC 4W8, 1200 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: P
authors.initials: P
authors.lastname: Bercik
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000382:microbiology* / Q000523:psychology; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D003106:Colon / Q000294:innervation / Q000382:microbiology*; D003345:Corticosterone / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D064806:Dysbiosis / Q000378:metabolism / Q000382:microbiology* / Q000523:psychology; D000069196:Gastrointestinal Microbiome / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006624:Hippocampus / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008426:Maternal Deprivation; D051379:Mice; D023421:Models, Animal; D009197:Myenteric Plexus; D009638:Norepinephrine / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism / Q000382:microbiology* / Q000523:psychology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012336:RNA, Ribosomal, 16S; D012701:Serotonin; D002097:C-Reactive Protein; D009195:Peroxidase; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine