Ingestion of <i>Lactobacillus</i> strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

Proceedings of the National Academy of Sciences of the United States of America - Tập 108 Số 38 - Trang 16050-16055 - 2011
Javier A. Bravo1, Paul Forsythe2,3, Marianne V. Chew3, Emily Escaravage3, Hélène M. Savignac4,5, Timothy G. Dinan6,7, John Bienenstock8,3, John F. Cryan9,10,5
1Laboratory of NeuroGastroenterology, Alimentary Pharmabiotic Centre,
2Medicine, and
3The McMaster Brain–Body Institute, St. Joseph's Healthcare, Hamilton, ON, Canada L8N 4A6; and Departments of
4Laboratory of NeuroGastroenterology, Alimentary Pharmabiotic Centre,; School of Pharmacy, and Departments of
5School of Pharmacy, and Departments of
6Laboratory of NeuroGastroenterology, Alimentary Pharmabiotic Centre,; Psychiatry and
7Psychiatry, and
8Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada L8S 4L8
9Anatomy, University College Cork, Cork, Ireland;
10Anatomy, University College Cork, Cork, Ireland;; Laboratory of NeuroGastroenterology, Alimentary Pharmabiotic Centre,; School of Pharmacy, and Departments of

Tóm tắt

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.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 108 Số 38

16050-16055

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