title: Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats.
abstract: OBJECTIVE
  Establishment of the gut microbiota is one of the most important events in early life and emerging evidence indicates that the gut microbiota influences several aspects of brain functioning, including reactivity to stress. To better understand how the gut microbiota contributes to a vulnerability to the stress-related psychiatric disorders, we investigated the relationship between the gut microbiota, anxiety-like behavior and HPA axis activity in stress-sensitive rodents. We also analyzed the monoamine neurotransmitters in the brain upper structures involved in the regulation of stress and anxiety.
  
  
  METHODS
  Germfree (GF) and specific pathogen free (SPF) F344 male rats were first subjected to neurological tests to rule out sensorimotor impairments as confounding factors. Then, we examined the behavior responses of rats to social interaction and open-field tests. Serum corticosterone concentrations, CRF mRNA expression levels in the hypothalamus, glucocorticoid receptor (GR) mRNA expression levels in the hippocampus, and monoamine concentrations in the frontal cortex, hippocampus and striatum were compared in rats that were either exposed to the open-field stress or not.
  
  
  RESULTS
  GF rats spent less time sniffing an unknown partner than SPF rats in the social interaction test, and displayed a lower number of visits to the aversive central area, and an increase in latency time, time spent in the corners and number of defecations in the open-field test. In response to the open-field stress, serum corticosterone concentrations were 2.8-fold higher in GF than in SPF rats. Compared to that of SPF rats, GF rats showed elevated CRF mRNA expression in the hypothalamus and reduced GR mRNA expression in the hippocampus. GF rats also had a lower dopaminergic turnover rate in the frontal cortex, hippocampus and striatum than SPF rats.
  
  
  CONCLUSIONS
  In stress-sensitive F344 rats, absence of the gut microbiota exacerbates the neuroendocrine and behavioral responses to acute stress and the results coexist with alterations of the dopaminergic turnover rate in brain upper structures that are known to regulate reactivity to stress and anxiety-like behavior.
authors.affiliation: INSERM, UMRS952 Physiopathologie des Maladies du Système Nerveux Central, F-75005 Paris, France; CNRS, UMR7224 Physiopathologie des Maladies du Système Nerveux Central, F-75005 Paris, France; UPMC, Physiopathologie des Maladies du Système Nerveux Central, F-75005 Paris, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Crumeyrolle-Arias
authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France; AgroParisTech, Micalis, F-78350 Jouy-en-Josas, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Jaglin
authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France; AgroParisTech, Micalis, F-78350 Jouy-en-Josas, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Bruneau
authors.affiliation: INRA, UR0909 Nurelice, Jouy-en-Josas, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Vancassel
authors.affiliation: Institut Pasteur, Plateforme Imagerie Dynamique, Paris, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Cardona
authors.affiliation: INSERM, UMRS952 Physiopathologie des Maladies du Système Nerveux Central, F-75005 Paris, France; CNRS, UMR7224 Physiopathologie des Maladies du Système Nerveux Central, F-75005 Paris, France; UPMC, Physiopathologie des Maladies du Système Nerveux Central, F-75005 Paris, France; CNRS, Micalis, F-78350 Jouy-en-Josas, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Daugé
authors.affiliation: INSERM, UMRS952 Physiopathologie des Maladies du Système Nerveux Central, F-75005 Paris, France; CNRS, UMR7224 Physiopathologie des Maladies du Système Nerveux Central, F-75005 Paris, France; UPMC, Physiopathologie des Maladies du Système Nerveux Central, F-75005 Paris, France; CNRS, Micalis, F-78350 Jouy-en-Josas, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Naudon
authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France; AgroParisTech, Micalis, F-78350 Jouy-en-Josas, France. Electronic address: Sylvie.Rabot@jouy.inra.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rabot
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000378:metabolism / Q000382:microbiology*; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D008297:Male; D064307:Microbiota; D010913:Pituitary-Adrenal System / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012919:Social Behavior; D013315:Stress, Psychological / Q000150:complications / Q000382:microbiology*
chemical_list: D011965:Receptors, Glucocorticoid; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
keywords: Brain monoamines; Corticosterone; Corticotropin releasing factor; Dopamine; Germfree; Glucocorticoid receptor; Gut–brain interaction; Hypothalamic pituitary adrenal axis; Open-field