The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication

被引:842
作者
Bercik, P. [1 ]
Park, A. J. [1 ]
Sinclair, D. [1 ]
Khoshdel, A. [1 ]
Lu, J. [1 ]
Huang, X. [1 ]
Deng, Y. [1 ]
Blennerhassett, P. A. [1 ]
Fahnestock, M. [2 ]
Moine, D. [3 ]
Berger, B. [3 ]
Huizinga, J. D. [1 ]
Kunze, W. [1 ]
McLean, P. G. [4 ]
Bergonzelli, G. E. [4 ]
Collins, S. M. [1 ]
Verdu, E. F. [1 ]
机构
[1] McMaster Univ, Farncombe Family Digest Hlth Res Inst, Dept Med, Hamilton, ON L8S 4K1, Canada
[2] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON L8S 4K1, Canada
[3] Nestle Res Ctr, Bioanalyt Sci Dept, CH-1000 Lausanne, Switzerland
[4] Nestle Res Ctr, Digest Hlth Nutr & Hlth Dept, CH-1000 Lausanne, Switzerland
关键词
behavior; brain-derived neurotrophic factor; gut-brain axis; probiotics; vagus; NEURONS; BEHAVIOR; INFLAMMATION; EXPRESSION; INFECTION; ANXIETY; MODELS; MICE;
D O I
10.1111/j.1365-2982.2011.01796.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
Background The probiotic Bifidobacterium longum NCC3001 normalizes anxiety-like behavior and hippocampal brain derived neurotrophic factor (BDNF) in mice with infectious colitis. Using a model of chemical colitis we test whether the anxiolytic effect of B. longum involves vagal integrity, and changes in neural cell function. Methods Mice received dextran sodium sulfate (DSS, 3%) in drinking water during three 1-week cycles. Bifidobacterium longum or placebo were gavaged daily during the last cycle. Some mice underwent subdiaphragmatic vagotomy. Behavior was assessed by step-down test, inflammation by myeloperoxidase (MPO) activity and histology. BDNF mRNA was measured in neuroblastoma SH-SY5Y cells after incubation with sera from B. longum- or placebo-treated mice. The effect of B. longum on myenteric neuron excitability was measured using intracellular microelectrodes. Key Results Chronic colitis was associated with anxiety-like behavior, which was absent in previously vagotomized mice. B. longum normalized behavior but had no effect on MPO activity or histological scores. Its anxiolytic effect was absent in mice with established anxiety that were vagotomized before the third DSS cycle. B. longum metabolites did not affect BDNF mRNA expression in SH-SY5Y cells but decreased excitability of enteric neurons. Conclusions & Inferences In this colitis model, anxiety-like behavior is vagally mediated. The anxiolytic effect of B. longum requires vagal integrity but does not involve gut immuno-modulation or production of BDNF by neuronal cells. As B. longum decreases excitability of enteric neurons, it may signal to the central nervous system by activating vagal pathways at the level of the enteric nervous system.
引用
收藏
页码:1132 / E544
页数:9
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