The gut microbiome regulates memory function

The mammalian gastrointestinal tract contains a diverse ecosystem of microbial species collectively making up the gut microbiota. 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) alters the gut microbiota 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. 16S rRNA gene sequencing of the fecal and cecal microbiota reveals that early life SSB consumption alters the relative abundance of various bacterial taxa. In particular, SSB elevates fecal operational taxonomic units within the genus Parabacteroides, which negatively correlate with memory task performance. Additional results reveal that transferred enrichment of Parabacteroides species P. distasonis and P. johnsonii in adolescent rats 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 bacterial alterations with memory impairment. Collectively these results identify a role for microbiota dysbiosis in mediating the negative effects of early life unhealthy dietary factors on neurocognitive outcomes.