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Common xenobiotics modulate gut microbial responses to low‑calorie sweeteners in vitro
The role of gut microbiota in the adverse effects associated with low-calorie sweeteners is a growing area of research. This study examines the interactions between 25 diverse gut bacterial strains and 39 widely used sweeteners, shedding light on their individual effects and on their interactions with four commonly consumed substances: advantame, caffeine, vanillin, and duloxetine.
Findings reveal that approximately 75% of the sweeteners tested affected at least one strain of bacteria. Notably, more than 100 significant interactions emerged between the sweeteners and the four co-consumed compounds. The combination of isosteviol, a frequently used sweetener, and duloxetine, an antidepressant, was particularly significant; this pairing led to a synergistic inhibition of two critical bacterial strains: Roseburia intestinalis, associated with glucose regulation, and Parabacteroides merdae, known for its role in maintaining a healthy microbiome.
Advanced analyses, including proteomic, metabolomic, and genetic evaluations, highlighted changes in small-molecule transport that underpin the observed sweetener-drug synergy. Additionally, the pairing influenced the metabolism of a synthetic gut bacterial community, resulting in heightened toxicity to HeLa cells and altered cytokine secretion (specifically IL-6 and IL-8) in Caco-2 cells, which are linked to inflammatory responses. These results underscore the necessity for additional research to explore the complex interactions between low-calorie sweeteners and common xenobiotics, given their potential implications for health. [NPID: Artificial sweeteners, microbiota, interactions, low-calorie sweeteners, xenobiotics]
Year: 2026
