Normal gut microbiota modulates brain development and behavior

被引:2342
作者
Heijtza, Rochellys Diaz [1 ,3 ]
Wang, Shugui [4 ]
Anuar, Farhana [2 ]
Qian, Yu [1 ,3 ]
Bjorkholm, Britta [2 ]
Samuelsson, Annika [2 ]
Hibberd, Martin L. [4 ]
Forssberg, Hans [3 ,5 ]
Pettersson, Sven [2 ,4 ]
机构
[1] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden
[2] Karolinska Inst, Dept Microbiol Cell & Tumor Biol, S-17177 Stockholm, Sweden
[3] Stockholm Brain Inst, S-17177 Stockholm, Sweden
[4] Genome Inst Singapore, Singapore 138672, Singapore
[5] Karolinska Inst, Dept Womens & Childrens Hlth, S-17176 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
developmental programming; microbiome; basal ganglia; cognitive behavior; synapse; INNATE IMMUNITY; VAGUS NERVE; EXPRESSION; ANXIETY; MECHANISMS; MICROFLORA; MICE; RATS; STIMULATION; DEPRESSION;
D O I
10.1073/pnas.1010529108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.
引用
收藏
页码:3047 / 3052
页数:6
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