title: Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve.
abstract: There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABA(B1b) mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABA(Aα2) mRNA expression in the prefrontal cortex and amygdala, but increased GABA(Aα2) in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression.
authors.affiliation: Laboratory of NeuroGastroenterology, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Bravo
authors.forename: Paul
authors.initials: P
authors.lastname: Forsythe
authors.forename: Marianne V
authors.initials: MV
authors.lastname: Chew
authors.forename: Emily
authors.initials: E
authors.lastname: Escaravage
authors.forename: Hélène M
authors.initials: HM
authors.lastname: Savignac
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Dinan
authors.forename: John
authors.initials: J
authors.lastname: Bienenstock
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
mesh_terms: D054458:Amplified Fragment Length Polymorphism Analysis; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D004269:DNA, Bacterial / Q000235:genetics; D003863:Depression / Q000503:physiopathology; D004644:Emotions / Q000502:physiology*; D005334:Fever / Q000097:blood / Q000382:microbiology / Q000503:physiopathology; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D017403:In Situ Hybridization; D007778:Lactobacillus / Q000235:genetics / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018079:Receptors, GABA / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics; D018080:Receptors, GABA-B / Q000235:genetics; D013045:Species Specificity; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology* / Q000601:surgery
chemical_list: D004269:DNA, Bacterial; D012333:RNA, Messenger; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D003345:Corticosterone