Department of Physiology and Pharmacology, Sapienza University, Rome, Italy.
Center for Life Nanoscience Istituto Italiano di Tecnologia@Sapienza, Rome, Italy.
Commun Biol. 2022 May 31;5(1):517. doi: 10.1038/s42003-022-03468-9.
Gut microorganisms and the products of their metabolism thoroughly affect host brain development, function and behavior. Since alterations of brain plasticity and cognition have been demonstrated upon motor, sensorial and social enrichment of the housing conditions, we hypothesized that gut microbiota and metabolome could be altered by environmental stimuli, providing part of the missing link among environmental signals and brain effects. In this preliminary study, metagenomic and metabolomic analyses of mice housed in different environmental conditions, standard and enriched, identify environment-specific microbial communities and metabolic profiles. We show that mice housed in an enriched environment have distinctive microbiota composition with a reduction in gut bacterial richness and biodiversity and are characterized by a metabolomic fingerprint with the increase of formate and acetate and the decrease of bile salts. We demonstrate that mice treated with a mixture of formate and acetate recapitulate some of the brain plasticity effects modulated by environmental enrichment, such as hippocampal neurogenesis, neurotrophin production, short-term plasticity and cognitive behaviors, that can be further exploited to decipher the mechanisms involved in experience-dependent brain plasticity.
肠道微生物及其代谢产物会深刻影响宿主大脑的发育、功能和行为。由于改变生活环境中的运动、感官和社交刺激可以改变大脑的可塑性和认知能力，我们假设肠道微生物群和代谢组可以通过环境刺激发生改变，为环境信号和大脑效应之间缺失的环节提供部分解释。在这项初步研究中，对生活在不同环境条件（标准和丰富）下的小鼠进行了宏基因组和代谢组分析，确定了环境特异性的微生物群落和代谢特征。结果表明，生活在丰富环境中的小鼠具有独特的微生物群落组成，肠道细菌丰富度和多样性降低，其代谢组学特征表现为甲酸盐和乙酸盐增加，胆盐减少。我们还证明，用甲酸盐和乙酸盐混合物处理的小鼠可以再现环境丰富化调节的一些大脑可塑性效应，如海马神经发生、神经营养因子产生、短期可塑性和认知行为，这些效应可以进一步被利用来解析经验依赖性大脑可塑性的相关机制。
