Effects of Non-Nutritive Artificial Sweeteners on Gut Microbiota and Host Metabolism and Health-Related Outcomes: A Review

As obesity, diabetes and other diet-related metabolic disorders continue to rise, non-nutritive artificial sweeteners (NASs) are widely used as sugar substitutes in free-sugar reduction and weight-management strategies, but their effects on the gut microbiota, host metabolism and related health outcomes remain debated. To clarify this evidence landscape, this review synthesizes current knowledge on the effects of major NAS on the gut microbiota and host metabolic and health-related outcome. A bibliometric analysis was conducted to characterize the development, knowledge structure and thematic evolution of this research area. For the eight NAS exposure categories included in this review (saccharin, cyclamate, aspartame, acesulfame potassium, sucralose, neotame, neohesperidin dihydrochalcone and mixed NAS), we performed a compound-specific analysis integrating physicochemical characteristics, regulatory status, and research findings from in vitro, ex vivo, animal and human studies on gut microbiota alterations, host metabolic and health-related outcomes. These findings were further compared through four interpretive dimensions: exposure conditions, research model background, outcome assessment and interpretation of discordant results. Current research evidence does not support a class-wide conclusion that NAS are uniformly harmful or safe. To make research findings searchable, we developed the NAS-MAP knowledge graph, an interactive non-nutritive artificial sweetener–microbiota-associated phenotype knowledge graph. Overall, this review consolidates current knowledge, clarifies the sources of inconsistent findings, and provides a framework for more mechanistically informative studies, standardized evidence reporting, and more precise sweetener-, exposure- and population-specific dietary and public health guidance.