Laboratory of NeuroGastroenterology, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16050-5. doi: 10.1073/pnas.1102999108. Epub 2011 Aug 29.
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.
越来越多的证据表明肠道共生菌群对中枢神经系统(CNS)有影响,但尚不清楚鼠李糖乳杆菌等乳酸菌是否对正常健康动物的中枢神经系统神经递质受体有直接影响。GABA 是中枢神经系统主要的抑制性神经递质,在调节许多生理和心理过程中起着重要作用。中枢 GABA 受体表达的改变与焦虑和抑郁的发病机制有关,焦虑和抑郁与功能性肠病高度共病。在这项工作中,我们表明,慢性给予鼠李糖乳杆菌(JB-1)治疗会导致大脑中 GABA(B1b)mRNA 出现区域依赖性改变,皮层区域(扣带回和额前皮质)增加,而海马、杏仁核和蓝斑减少,与对照组相比。此外,鼠李糖乳杆菌(JB-1)降低了前额叶皮层和杏仁核中的 GABA(Aα2)mRNA 表达,但增加了海马中的 GABA(Aα2)。重要的是,鼠李糖乳杆菌(JB-1)降低了应激诱导的皮质酮和焦虑和抑郁相关行为。此外,迷走神经切断的小鼠没有发现神经化学和行为效应,这表明迷走神经是暴露于肠道的细菌与大脑之间主要的调节性固有通讯途径。这些发现共同强调了细菌在肠道-大脑轴的双向通讯中的重要作用,并表明某些生物体可能被证明是治疗与应激相关的疾病(如焦虑和抑郁)的有用辅助手段。