Effect of Human Infant Gut Microbiota on Mouse Behavior, Dendritic Complexity, and Myelination

The mammalian gut microbiome influences numerous developmental processes. In human infants it has been linked with cognition, social skills, hormonal responses to stress, and brain connectivity. Yet, these associations are not necessarily causal. The present study tested whether two microbial stool communities, common in human infants, affected behavior, myelination, dendritic morphology, and spine density when used to colonize mouse models. Humanized animals were more like specific-pathogen free mice than germ-free mice for most phenotypes, although in males, both humanized groups were less social. Both humanized groups had thinner myelin sheaths in the hippocampus, than did germ-free animals. Humanized animals were similar to each other except for dendritic morphology and spine density where one group had greater dendritic length in the prefrontal cortex, greater dendritic volume in the nucleus accumbens, and greater spine density in both regions, compared to the other. Results add to a body of literature suggesting the gut microbiome impacts brain development.

哺乳动物肠道微生物组（gut microbiome）可调控诸多发育进程。在人类婴儿群体中，该微生物组已被证实与认知能力、社交技能、应激激素反应以及大脑连接性存在关联。然而，此类关联未必具有因果性。本研究针对两种常见于人类婴儿的粪便微生物群落展开实验，探究其通过定植构建小鼠模型后，是否会对小鼠行为、髓鞘形成（myelination）、树突形态（dendritic morphology）以及突触棘密度（spine density）产生影响。在多数表型层面，人源化小鼠更接近无特定病原体（specific-pathogen free）小鼠，而非无菌（germ-free）小鼠；但在雄性个体中，两个人源化组的社交能力均偏弱。两个人源化组小鼠的海马体髓鞘均较无菌小鼠更薄。除树突形态与突触棘密度外，两个人源化组小鼠的表型较为相似：相较于另一组，其中一组小鼠的前额叶皮层（prefrontal cortex）树突长度更长、伏隔核（nucleus accumbens）树突体积更大，且上述两个脑区的突触棘密度均更高。本研究结果进一步充实了肠道微生物组可影响大脑发育的相关研究文献。