Reduced anxiety-like behavior and central neurochemical change in germ-free mice.
BACKGROUND
There is increasing interest in the gut-brain axis and the role intestinal microbiota may play in communication between these two systems. Acquisition of intestinal microbiota in the immediate postnatal period has a defining impact on the development and function of the gastrointestinal, immune, neuroendocrine and metabolic systems. For example, the presence of gut microbiota regulates the set point for hypothalamic-pituitary-adrenal (HPA) axis activity.


METHODS
We investigated basal behavior of adult germ-free (GF), Swiss Webster female mice in the elevated plus maze (EPM) and compared this to conventionally reared specific pathogen free (SPF) mice. Additionally, we measured brain mRNA expression of genes implicated in anxiety and stress-reactivity.


RESULTS
Germ-free mice, compared to SPF mice, exhibited basal behavior in the EPM that can be interpreted as anxiolytic. Altered GF behavior was accompanied by a decrease in the N-methyl-D-aspartate receptor subunit NR2B mRNA expression in the central amygdala, increased brain-derived neurotrophic factor expression and decreased serotonin receptor 1A (5HT1A) expression in the dentate granule layer of the hippocampus.


CONCLUSIONS
We conclude that the presence or absence of conventional intestinal microbiota influences the development of behavior, and is accompanied by neurochemical changes in the brain.
Brain-Body Institute, St. Joseph's Healthcare, Hamilton, ON, Canada.
K M
KM
Neufeld
N
N
Kang
J
J
Bienenstock
J A
JA
Foster
D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology; D001923:Brain Chemistry; D003345:Corticosterone / Q000097:blood; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D015870:Gene Expression; D005856:Germ-Free Life; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D054892:Metagenome; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological
D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D003345:Corticosterone