Abstract: Sweeteners cannot completely replace the satisfaction provided by sugars, even though they offer a similar flavor perception and much higher sweetness intensity than sugars. Clarifying the biological mechanism of this phenomenon is important to improve the functional evaluation system for sweeteners and promote sweetener innovations. Herein, we review the research progress on the difference in the behavioral preferences of animals, the activity of brain regions and the activation patterns of the gut-brain axis induced by sugars and sweeteners, and we uncover the underlying reason why the brain distinguishes sugars from sweeteners, causing differences in individual behavioral preferences. Moreover, we propose that animal behavior, neural activity in brain regions, and the capacity to activate key receptors can be used to evaluate the gut-brain axis effects of sweeteners, which will provide a reference for innovative developments in the field of sweeteners.

Key words: sugar; sweetener; gut-brain axis; behavioral preferences; neural activity