The gut microbiome regulates memory function.

The mammalian gastrointestinal tract contains a diverse ecosystem of microbial species collectively making up the gut microbiome. Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Consumption of unhealthy yet palatable dietary factors associated with obesity and metabolic dysfunction (e.g., saturated fat, added sugar) produces microbiota dysbiosis and negatively impacts neurocognitive function, particularly when consumed during early life developmental periods. Here we explore whether excessive early life consumption of added sugars negatively impacts neurocognitive development via the gut microbiome. Using a rodent model of habitual sugar-sweetened beverage (SSB) consumption during the adolescent stage of development, we first show that excessive early life sugar intake impairs hippocampal-dependent memory function when tested during adulthood while preserving other neurocognitive domains. Gut microbiome genomic sequencing analyses reveal that early life SSB consumption alters the abundance of various bacterial populations, including elevations in operational taxonomic units within the genus Parabacteroides (P. distasonis and P. johnsonii) whose abundance negatively correlated with memory task performance. Additional results reveal that in vivo Parabacteroides enrichment of cultured P. distasonis and P. johnsonii bacterial species in adolescent rats severely impairs memory function during adulthood. Hippocampus transcriptome analyses identify gene expression alterations in neurotransmitter synaptic signaling, intracellular kinase signaling, metabolic function, neurodegenerative disease, and dopaminergic synaptic signaling-associated pathways as potential mechanisms linking microbiome outcomes with memory impairment. Collectively these results identify microbiota dysbiosis as a mechanism through which early life unhealthy dietary patterns negatively impact neurocognitive outcomes.哺乳动物胃肠道内存在由多样微生物种群共同构成的复杂生态系统，即肠道微生物组（gut microbiome）。新兴研究证据表明，肠道菌群与神经认知发育之间存在关键关联。与肥胖及代谢功能障碍相关的不健康但适口的饮食因子（例如饱和脂肪、添加糖）会引发菌群失调，并对神经认知功能产生负面影响，尤其在生命早期发育阶段摄入此类饮食时。本研究旨在探讨生命早期过量摄入添加糖是否会通过肠道菌群损害神经认知发育。本研究采用青春期阶段习惯性饮用含糖饮料（sugar-sweetened beverage, SSB）的啮齿类动物模型，实验首先证实：成年后测试时，生命早期过量糖摄入会损害海马依赖型记忆功能，同时保留其他神经认知领域的功能。肠道菌群基因组测序分析显示，生命早期饮用含糖饮料会改变多种细菌种群的丰度，包括副杆菌属（Parabacteroides）内的操作分类单元（operational taxonomic units, OTU）丰度升高，该属的P. distasonis与P. johnsonii的丰度与记忆任务表现呈负相关。额外实验结果表明，在青春期大鼠体内富集培养的P. distasonis和P. johnsonii菌株，会严重损害成年后的记忆功能。海马转录组分析发现，神经递质突触信号、细胞内激酶信号、代谢功能、神经退行性疾病以及多巴胺能突触信号相关通路的基因表达发生改变，这可能是连接菌群变化与记忆损害的潜在机制。综上，本研究结果证实，菌群失调是生命早期不健康饮食模式损害神经认知结局的潜在机制。