Sweetener synapse : Exploring non-nutritive sweeteners' role in zebrafish glucose homeostasis

The use of non-nutritive sweeteners as calorie-free substitutes for sugar has gained more attention. The rising prevalence of metabolic disorders and neurological dysfunctions potentially associated with non-nutritive sweeteners has prompted increased scrutiny of these sugar substitutes. This study investigated the neuroendocrine and metabolic effects of chronic exposure to sucralose and stevia, both individually and in combination, using Danio rerio as a model organism. Adult zebrafish were subjected to environmentally relevant concentrations of these sweeteners, followed by a comprehensive battery of neurobehavioral assays, including scototaxis, agonistic behavior assessment, social interaction tests, and novel object recognition paradigms. Biochemical analyses encompassed acetylcholinesterase activity, serotonergic modulation, and hypothalamic-pituitary-interrenal axis function via cortisol quantification. Metabolic perturbations were evaluated through glucose tolerance tests, body mass index calculations, and metabolic enzyme activity assays. Additionally, gut microbiome alterations were assessed, focusing on Lactobacillus and Bifidobacterium populations. Results demonstrated a significant anxiogenic and depressogenic effect, cognitive impairment, and heightened aggression in exposed specimens. These behavioral abnormalities correlated with decreased acetylcholinesterase (AChE) activity, serotonin depletion, and elevated cortisol levels, indicative of neurotoxicity and hypothalamic-pituitary-adrenal axis dysregulation. Metabolic disruptions manifested as hyperglycemia, increased adiposity, and altered enzymatic profiles, suggesting a predisposition to obesity and glucose intolerance. Notably, shifts in gut microbiota composition, particularly affecting serotonin and short-chain fatty acid production, potentially exacerbated the observed neurotoxic effects. The study revealed that combined exposure to sucralose and stevia elicited synergistic adverse outcomes, surpassing the effects observed in individual exposure groups. These findings underscore the potential risks associated with such sweetener consumption and highlight the need for further investigation into their long-term health implications.