title: Structural & functional consequences of chronic psychosocial stress on the microbiome & host.
abstract: BACKGROUND
  Given the lasting impact of psychological distress on behavior, along with the role of the microbiome in neurobehavioral development, we sought to examine the relationship between the microbiota and stress-induced behavioral deficits.
  
  
  METHODS
  Male C57BL/6 mice exposed to chronic social defeat were subjected to behavioral analysis and profiling of the intestinal microbiome. Mice were also analyzed for phenotypic and functional immune changes. A computational approach on 16S rRNA marker gene sequences was used to predict functional changes in the metagenome as a consequence of structural shifts in the microbiota.
  
  
  RESULTS
  Chronic social defeat induced behavioral changes that were associated with reduced richness and diversity of the gut microbial community, along with distinct shifts at the level of operational taxonomic units (OTU) across phyla. The degree of deficits in social, but not exploratory behavior was correlated with group differences between the microbial community profile. In silico analysis predicted a shift in the functional profile of the microbiome: defeated mice exhibited reduced functional diversity and a lower prevalence of pathways involved in the synthesis and metabolism of neurotransmitter precursors and short-chain fatty acids. Defeated mice also exhibited sustained alterations in dendritic cell activation, and transiently elevated levels of IL-10+ T regulatory cells that were suppressed over time.
  
  
  CONCLUSIONS
  This study indicates that stress-induced disruptions in neurologic function are associated with altered immunoregulatory responses and complex OTU-level shifts in the microbiota. It is thus suggested that a dysbiotic state, along with specific changes in microbial markers, may predict the onset of adverse neurocognitive deficits commonly observed following exposure to severe stressors. The data also predict novel pathways that might underlie microbiota-mediated effects on brain and behavior, thus presenting targets for investigations into mechanisms and potential therapy.
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster University, 1280 Main Street West Hamilton, Ontario L8S 4L8, Canada; McMaster Brain-Body Institute, St. Joseph's Healthcare, 50 Charlton Avenue East Hamilton, Ontario L8N 4A6, Canada.
authors.forename: Aadil
authors.initials: A
authors.lastname: Bharwani
authors.affiliation: McMaster Brain-Body Institute, St. Joseph's Healthcare, 50 Charlton Avenue East Hamilton, Ontario L8N 4A6, Canada.
authors.forename: M Firoz
authors.initials: MF
authors.lastname: Mian
authors.affiliation: Department of Psychiatry & Behavioral Neurosciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada; McMaster Brain-Body Institute, St. Joseph's Healthcare, 50 Charlton Avenue East Hamilton, Ontario L8N 4A6, Canada.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Foster
authors.affiliation: Department of Medicine, McMaster University, 1280 Main Street West Hamilton, Ontario L8S 4K1, Canada; Farncombe Family Digestive Health Research Institute, 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Surette
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster University, 1280 Main Street West Hamilton, Ontario L8S 4L8, Canada; McMaster Brain-Body Institute, St. Joseph's Healthcare, 50 Charlton Avenue East Hamilton, Ontario L8N 4A6, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Bienenstock
authors.affiliation: Department of Medicine, McMaster University, 1280 Main Street West Hamilton, Ontario L8S 4K1, Canada; Firestone Institute for Respiratory Health, St. Joseph's Healthcare, 50 Charlton Avenue East Hamilton, Ontario L8N 4A6, Canada; McMaster Brain-Body Institute, St. Joseph's Healthcare, 50 Charlton Avenue East Hamilton, Ontario L8N 4A6, Canada. Electronic address: forsytp@mcmaster.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Forsythe
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002478:Cells, Cultured; D002908:Chronic Disease; D004291:Dominance-Subordination; D005106:Exploratory Behavior / Q000502:physiology; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000502:physiology*; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012919:Social Behavior; D013315:Stress, Psychological / Q000276:immunology / Q000382:microbiology* / Q000523:psychology*
chemical_list: D016753:Interleukin-10
keywords: Behavior; Chronic social defeat; Functional metagenome; Gut microbiota; Immune regulation; Psychosocial stress