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

神经化学 神经科学 前额叶皮质 内分泌学 扁桃形结构 海马体 生物 内科学 蓝斑 迷走神经 神经递质 受体 加巴能 γ-氨基丁酸受体 谷氨酸脱羧酶 γ-氨基丁酸 医学 中枢神经系统 认知 刺激
作者
Javier A. Bravo,Paul Forsythe,Marianne V. Chew,Emily Escaravage,Hélène M. Savignac,Timothy G. Dinan,John Bienenstock,John F. Cryan
出处
期刊:Proceedings of the National Academy of Sciences of the United States of America [Proceedings of the National Academy of Sciences]
卷期号:108 (38): 16050-16055 被引量:2235
标识
DOI:10.1073/pnas.1102999108
摘要

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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