title: Growing up in a Bubble: Using Germ-Free Animals to Assess the Influence of the Gut Microbiota on Brain and Behavior.
abstract: There is a growing recognition of the importance of the commensal intestinal microbiota in the development and later function of the central nervous system. Research using germ-free mice (mice raised without any exposure to microorganisms) has provided some of the most persuasive evidence for a role of these bacteria in gut-brain signalling. Key findings show that the microbiota is necessary for normal stress responsivity, anxiety-like behaviors, sociability, and cognition. Furthermore, the microbiota maintains central nervous system homeostasis by regulating immune function and blood brain barrier integrity. Studies have also found that the gut microbiota influences neurotransmitter, synaptic, and neurotrophic signalling systems and neurogenesis. The principle advantage of the germ-free mouse model is in proof-of-principle studies and that a complete microbiota or defined consortiums of bacteria can be introduced at various developmental time points. However, a germ-free upbringing can induce permanent neurodevelopmental deficits that may deem the model unsuitable for specific scientific queries that do not involve early-life microbial deficiency. As such, alternatives and complementary strategies to the germ-free model are warranted and include antibiotic treatment to create microbiota-deficient animals at distinct time points across the lifespan. Increasing our understanding of the impact of the gut microbiota on brain and behavior has the potential to inform novel management strategies for stress-related gastrointestinal and neuropsychiatric disorders.
authors.affiliation: APC Microbiome Institute (Ms Luczynski, Dr McVey Neufeld, Ms Oriach, Dr Clarke, Dr Dinan, and Dr Cryan), Department of Psychiatry and Neurobehavioral Science (Ms Oriach, Dr Clarke, and Dr Dinan), and Department of Anatomy and Neuroscience (Dr Cryan), University College Cork, Cork, Ireland.
authors.forename: Pauline
authors.initials: P
authors.lastname: Luczynski
authors.affiliation: APC Microbiome Institute (Ms Luczynski, Dr McVey Neufeld, Ms Oriach, Dr Clarke, Dr Dinan, and Dr Cryan), Department of Psychiatry and Neurobehavioral Science (Ms Oriach, Dr Clarke, and Dr Dinan), and Department of Anatomy and Neuroscience (Dr Cryan), University College Cork, Cork, Ireland.
authors.forename: Karen-Anne
authors.initials: KA
authors.lastname: McVey Neufeld
authors.affiliation: APC Microbiome Institute (Ms Luczynski, Dr McVey Neufeld, Ms Oriach, Dr Clarke, Dr Dinan, and Dr Cryan), Department of Psychiatry and Neurobehavioral Science (Ms Oriach, Dr Clarke, and Dr Dinan), and Department of Anatomy and Neuroscience (Dr Cryan), University College Cork, Cork, Ireland.
authors.forename: Clara Seira
authors.initials: CS
authors.lastname: Oriach
authors.affiliation: APC Microbiome Institute (Ms Luczynski, Dr McVey Neufeld, Ms Oriach, Dr Clarke, Dr Dinan, and Dr Cryan), Department of Psychiatry and Neurobehavioral Science (Ms Oriach, Dr Clarke, and Dr Dinan), and Department of Anatomy and Neuroscience (Dr Cryan), University College Cork, Cork, Ireland.
authors.forename: Gerard
authors.initials: G
authors.lastname: Clarke
authors.affiliation: APC Microbiome Institute (Ms Luczynski, Dr McVey Neufeld, Ms Oriach, Dr Clarke, Dr Dinan, and Dr Cryan), Department of Psychiatry and Neurobehavioral Science (Ms Oriach, Dr Clarke, and Dr Dinan), and Department of Anatomy and Neuroscience (Dr Cryan), University College Cork, Cork, Ireland.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Dinan
authors.affiliation: APC Microbiome Institute (Ms Luczynski, Dr McVey Neufeld, Ms Oriach, Dr Clarke, Dr Dinan, and Dr Cryan), Department of Psychiatry and Neurobehavioral Science (Ms Oriach, Dr Clarke, and Dr Dinan), and Department of Anatomy and Neuroscience (Dr Cryan), University College Cork, Cork, Ireland. J.Cryan@ucc.ie.
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000254:growth & development* / Q000502:physiology*; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D005856:Germ-Free Life / Q000502:physiology*
keywords: cognitive dysfunction; germ-free mouse; microbiota-gut-brain axis; social development; stress response