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DOES EARLY-LIFE EXPOSURE TO NON-NUTRITIVE SWEETENERS HAVE LONG-TERM EFFECTS?

Abstract

Obesity remains one of the most significant public health challenges in the United States and globally, affecting approximately 42 percent of adults and nearly 20 percent of children (Bryan et al., 2021). Excess consumption of sugar sweetened foods and beverages is widely recognized as a major contributor to rising obesity rates and associated metabolic disorders (Malik and Hu, 2022). In response, non nutritive sweeteners have been increasingly adopted as low calorie alternatives designed to reduce caloric intake while maintaining palatability. Between 1999 and 2012, consumption of non nutritive sweeteners among children rose from 8.7 percent to 25.1 percent, reflecting their growing prevalence in modern diets (Sylvetsky et al., 2017). Despite their widespread use, the long term physiological and behavioral consequences of non nutritive sweetener exposure, particularly during early development, remain poorly understood. Emerging research suggests that these compounds may influence metabolic regulation, neural reward pathways, and gut microbiota composition, thereby producing lasting changes in behavior and physiology (Suez et al., 2014; Yang, 2010). Additionally, non nutritive sweeteners may disrupt learned associations between sweetness and caloric intake, potentially altering feeding behavior and energy regulation (Davidson and Swithers, 2004; Swithers and Davidson, 2008). The High Runner mouse selection experiment provides a powerful model for examining how genetic background interacts with environmental exposures. High Runner mice have been selectively bred for high voluntary wheel running behavior across more than one hundred generations and exhibit elevated activity levels along with distinct physiological traits compared to Control mice (Careau et al., 2013). In the present study, juvenile female High Runner and Control mice were exposed for three weeks following weaning to one of four drinking solutions including water, sucrose, saccharin, or sucralose. After an eight week washout period, mice underwent behavioral testing using the open field assay. Behavioral outcomes were quantified using total distance traveled, total number of movement bouts, and distance traveled in the center of the arena. In addition, physiological stress indicators including fecal pellet production and urine output were measured. Contrary to expectations, High Runner mice exhibited reduced locomotor activity and reduced center exploration compared to Control mice across all treatments. Early life exposure to sweeteners, particularly saccharin, was associated with decreased exploratory behavior and increased anxiety related responses. These findings suggest that early dietary exposure to non nutritive sweeteners can produce long term behavioral changes that are influenced by genetic background and environmental context.