Background

Early life sugar consumption impairs memory function and metabolic outcomes in rats. We sought to determine whether the gut microbiome mechanistically contributes to these outcomes.

Methods

Exp. 1: Male rats had free access to food, water, and either [1] an 11% sugar solution or [2] an extra water bottle (controls) for the entire juvenile-adolescent period (PN27-60). Performance in a hippocampal-dependent contextual episodic memory task and metabolic outcomes were assessed. Fecal samples were collected for 16S rRNA genomic sequencing and linear regression modeling. Exp. 2: Juvenile rats underwent microbiome depletion by antibiotics followed by fecal transfer either from rats fed sugar solution during early-life or from control rats. An additional control group received saline gavage throughout both stages. Metabolic and memory testing commenced at PN60. Exp. 3: Modeling the design of Exp. 2, rats underwent antibiotic-based microbiome depletion followed by bacterial enrichment of two species within the genus Parabacteroides that are elevated by sugar consumption (P. distasonis and P. johnsonii).

Results

Early life sugar impaired hippocampal-dependent memory performance and glucose tolerance. Microbiome transfer from sugar-fed animals impaired memory function, but not glucose tolerance. Two bacteria species in Parabacteroides (P. distasonis and P. johnsonii) whose abundance negatively correlated with memory performance were elevated by sugar. Finally, bacterial enrichment of P. distasonis and P. johnsonii during early life impaired memory performance.

Conclusions

Early life sugar consumption impairs hippocampal-dependent memory in rats. These effects were likely related to alterations in the gut microbiome, as either fecal transfer from rats fed sugar during development or early life gut colonization with bacterial species elevated by dietary sugar impairs memory function. These findings identify a mechanistic link between dietary sugar and cognitive impairment.