There is growing evidence that repeated consumption of highly palatable, nutritionally poor "junk food" diets can produce deficits in cognition and behavioral control. We explored whether long-term junk-food diet exposure disrupts rats' ability to make adaptive choices about which foods to pursue based on (1) expected reward value (outcome devaluation test) and (2) cue-evoked reward expectations (Pavlovian-to-instrumental test). Rats were initially food restricted and trained on two distinct response-outcome contingencies (e.g., left press chocolate pellets, and right press sweetened condensed milk) and stimulus-outcome contingencies (e.g., white noise chocolate pellets, and clicker sweetened condensed milk). They were then given 6 weeks of unrestricted access to regular chow alone (controls) or chow and either 1 or 24 h access to junk food per day. Subsequent tests of decision making revealed that rats in both junk-food diet groups were impaired in selecting actions based on either expected food value or the presence of food-paired cues. These data demonstrate that chronic junk food consumption can disrupt the processes underlying adaptive control over food-seeking behavior. We suggest that the resulting dysregulation of food seeking may contribute to overeating and obesity.

Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Excessive consumption of sugar and other unhealthy dietary factors during early life developmental periods yields changes in the gut microbiome as well as neurocognitive impairments. However, it is unclear whether these two outcomes are functionally connected. Here we explore whether excessive early life consumption of added sugars negatively impacts memory function via the gut microbiome. Rats were given free access to a sugar-sweetened beverage (SSB) during the adolescent stage of development. Memory function and anxiety-like behavior were assessed during adulthood and gut bacterial and brain transcriptome analyses were conducted. Taxa-specific microbial enrichment experiments examined the functional relationship between sugar-induced microbiome changes and neurocognitive and brain transcriptome outcomes. Chronic early life sugar consumption impaired adult hippocampal-dependent memory function without affecting body weight or anxiety-like behavior. Adolescent SSB consumption during adolescence also altered the gut microbiome, including elevated abundance of two species in the genus Parabacteroides (P. distasonis and P. johnsonii) that were negatively correlated with hippocampal function. Transferred enrichment of these specific bacterial taxa in adolescent rats impaired hippocampal-dependent memory during adulthood. Hippocampus transcriptome analyses revealed that early life sugar consumption altered gene expression in intracellular kinase and synaptic neurotransmitter signaling pathways, whereas Parabacteroides microbial enrichment altered gene expression in pathways associated with metabolic function, neurodegenerative disease, and dopaminergic signaling. Collectively these results identify a role for microbiota "dysbiosis" in mediating the detrimental effects of early life unhealthy dietary factors on hippocampal-dependent memory function.

Low-calorie sweetener (LCS) consumption in children has increased dramatically due to its widespread presence in the food environment and efforts to mitigate obesity through sugar replacement. However, mechanistic studies on the long-term impact of early-life LCS consumption on cognitive function and physiological processes are lacking. Here, we developed a rodent model to evaluate the effects of daily LCS consumption (acesulfame potassium, saccharin, or stevia) during adolescence on adult metabolic, behavioral, gut microbiome, and brain transcriptomic outcomes. Results reveal that habitual early-life LCS consumption impacts normal postoral glucose handling and impairs hippocampal-dependent memory in the absence of weight gain. Furthermore, adolescent LCS consumption yielded long-term reductions in lingual sweet taste receptor expression and brought about alterations in sugar-motivated appetitive and consummatory responses. While early-life LCS consumption did not produce robust changes in the gut microbiome, brain region-specific RNA-Seq analyses reveal LCS-induced changes in collagen- and synaptic signaling-related gene pathways in the hippocampus and nucleus accumbens, respectively, in a sex-dependent manner. Collectively, these results reveal that habitual early-life LCS consumption has long-lasting implications for glucoregulation, sugar-motivated behavior, and hippocampal-dependent memory in rats, which may be based in part on changes in nutrient transporter, sweet taste receptor, and central gene pathway expression.