Early life consumption of a "processed" diet high in advanced glycation end products impairs memory function and alters the gut microbiome in rats

Abstract

Recent evidence indicates that “ultra-processed” foods constitute ~65% of total energy intake among children in the U.S. The impacts of excessive processed food consumption during development are poorly understood, in part because there are neither clear definitions of, nor a robust classification system accounting for, the complexity of food processing variables and how they interrelate in final food products. Heat treatment, a common form of food processing, can induce the chemical Maillard reaction and lead to foods rich in advanced glycation end products (AGEs). The neurocognitive implications of high levels of AGE consumption, particularly during early life, are unknown. Here, we used a rat model to evaluate the effects of adolescent consumption of a heat-treated diet high in AGEs on cognition and the gut microbiome in adulthood. In a series of studies, rats received either an otherwise healthy AGE-rich diet (AGE rats; AIN-93G diet heated at 160ºC for 60min) or a non-AGE-rich diet (CTL rats; AIN-93G diet without heat treatment) during adolescence (postnatal days 26-60). Metabolic, behavioral, and gut microbiome assessments were performed in adulthood. Results revealed that AGE rats exhibited hippocampal (HPC)-dependent memory deficits relative to CTL rats in the absence of altered body weight, body composition, glucose tolerance, and behavioral measures of anxiety. Administering a drug to break down AGEs (alagebrium; 1mg/kg/day) concomitantly with the heat-treated diet prevented memory impairments, supporting a causal role of AGEs in early life diet-induced HPC dysfunction. Microbiome sequencing analyses revealed that AGE rats had substantially reduced abundance of the bacterial genus Lactococcus relative to controls, and Lactococcus abundance was strongly correlated with memory performance. Administration of Lactococcus lactis by oral gavage (109 colony forming units/day) from PN 26-40 during exposure to the heat-treated diet rescued the AGE diet-induced memory impairments. Collective findings from this work identify a connection between a specific food processing variable (i.e., increased dietary AGEs through heat treatment), the gut microbiome, and impaired neurocognition. This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases under grant DK123423 (awarded to SEK and AAF); the National Institute on Aging through a Postdoctoral Ruth L. Kirschstein National Research Service Award under grant F32AG077932 (awarded to AMRH); and a National Science Foundation Graduate Research Fellowship (awarded to LT). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.