Early life Western diet-induced memory impairments and gut microbiome changes in female rats are long-lasting despite healthy dietary intervention

Abstract

Objective: Consumption of a Western diet during adolescence results in hippocampus (HPC)- dependent memory impairments and gut microbiome dysbiosis. Whether these adverse outcomes are reversible in adulthood following intervention with a healthy diet is unknown. Here we assessed the short- and long-term effects of adolescent consumption of a Western diet enriched with either sugar alone, or sugar and fat on metabolic outcomes, HPC-dependent memory, and gut microbiota. Methods: Adolescent female rats (PN 26) were fed a standard chow diet (CTL), a chow diet with access to 11% sugar solution (SUG), or a junk food cafeteria-style diet (CAF) containing a variety of fat- and/or sugar-enriched foods. During adulthood (PN 65+), metabolic outcomes, HPC-dependent memory, and gut microbial populations were evaluated both before and after a 5-week dietary intervention period where all groups were fed a diet of water standard chow. Results: Prior to the dietary intervention both the CAF and SUG groups demonstrated impaired HPC-dependent memory, increased adiposity, and altered gut microbial populations relative to controls. However, impaired peripheral glucose regulation was only observed in the SUG group. The dietary intervention reversed the metabolic dysfunction in both the CAF and SUG groups, whereas HPC-dependent memory impairments were reversed in the SUG, but not the CAF group. The composition of the gut microbiota remained distinct from controls in both groups after dietary intervention. Conclusions: While the metabolic impairments associated with adolescent cafeteria diet consumption are reversible in adulthood with dietary intervention, the HPC-dependent memory impairments and the gut microbiome dysbiosis persist.

Early-life low-calorie sweetener consumption disrupts glucose regulation, sugar-motivated behavior, and memory function in rats

“…Some experiments were conducted with a single LCS, ACE-K, as the representative sweetener given that this LCS is commonly consumed in human populations (2). Early life exposure to natural sugars yields sex-specific differences later in life (12,13,42), and thus prompted a direct comparison between male and female rats in our initial study. These differences are highlighted below only where overall significant effects or interactions involving sex were detected (results are otherwise plotted by sex in the supplementary data).…”

“…Novel Object in Context. Contextual episodic memory was assessed beginning at PN 63 (following 30 days of LCS consumption) using the hippocampal-dependent Novel Object in Context (NOIC) task, a timeframe and behavioral procedure adapted from (42). The NOIC procedure took place over 5-days, each day consisting of a 5-min session per animal.…”