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

Javier A. Bravo, Paul Forsythe, Marianne V. Chew, Emily Escaravage, Hélène M. Savignac, Timothy G. Dinan, John Bienenstock, and John F. Cryan
PNAS September 20, 2011 108 (38) 16050-16055; https://doi.org/10.1073/pnas.1102999108
Javier A. Bravo
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Paul Forsythe
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Marianne V. Chew
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Emily Escaravage
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Hélène M. Savignac
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Timothy G. Dinan
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John Bienenstock
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John F. Cryan
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  1. Edited by Todd R. Klaenhammer, North Carolina State University, Raleigh, NC, and approved July 27, 2011 (received for review February 27, 2011)

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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 GABAB1b 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 GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 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.

  • brain–gut axis
  • irritable bowel syndrome
  • probiotic
  • fear conditioning
  • cognition

Footnotes

  • ↵1J.A.B. and P.F. contributed equally to this work.

  • 2To whom correspondence may be addressed. E-mail: bienens{at}mcmaster.ca or j.cryan{at}ucc.ie.
  • Author contributions: J.A.B., P.F., M.V.C., H.M.S., T.G.D., J.B., and J.F.C. designed research; J.A.B., P.F., M.V.C., E.E., and H.M.S. performed research; J.A.B., P.F., H.M.S., J.B., and J.F.C. analyzed data; and J.A.B., P.F., T.G.D., J.B., and J.F.C. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1102999108/-/DCSupplemental.

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Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve
Javier A. Bravo, Paul Forsythe, Marianne V. Chew, Emily Escaravage, Hélène M. Savignac, Timothy G. Dinan, John Bienenstock, John F. Cryan
Proceedings of the National Academy of Sciences Sep 2011, 108 (38) 16050-16055; DOI: 10.1073/pnas.1102999108

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Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve
Javier A. Bravo, Paul Forsythe, Marianne V. Chew, Emily Escaravage, Hélène M. Savignac, Timothy G. Dinan, John Bienenstock, John F. Cryan
Proceedings of the National Academy of Sciences Sep 2011, 108 (38) 16050-16055; DOI: 10.1073/pnas.1102999108
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