Department of Medical Biochemistry, Faculty of Medicine, Near East University, Nicosia 99138, Cyprus.
Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Be'er Sheva 84105, Israel.
Int J Mol Sci. 2021 Sep 13;22(18):9863. doi: 10.3390/ijms22189863.
Despite having been tagged as safe and beneficial, recent evidence remains inconclusive regarding the status of artificial sweeteners and their putative effects on gut microbiota. Gut microorganisms are essential for the normal metabolic functions of their host. These microorganisms communicate within their community and regulate group behaviors via a molecular system termed quorum sensing (QS). In the present study, we aimed to study the effects of artificial sweeteners on this bacterial communication system. Using biosensor assays, biophysical protein characterization methods, microscale thermophoresis, swarming motility assays, growth assays, as well as molecular docking, we show that aspartame, sucralose, and saccharin have significant inhibitory actions on the Gram-negative bacteria -acyl homoserine lactone-based (AHL) communication system. Our studies indicate that these three artificial sweeteners are not bactericidal. Protein-ligand docking and interaction profiling, using LasR as a representative participating receptor for AHL, suggest that the artificial sweeteners bind to the ligand-binding pocket of the protein, possibly interfering with the proper housing of the native ligand and thus impeding protein folding. Our findings suggest that these artificial sweeteners may affect the balance of the gut microbial community via QS-inhibition. We, therefore, infer an effect of these artificial sweeteners on numerous molecular events that are at the core of intestinal microbial function, and by extension on the host metabolism.
尽管人工甜味剂被标记为安全且有益，但最近的证据仍然无法确定其地位及其对肠道微生物群的潜在影响。肠道微生物对于宿主的正常代谢功能至关重要。这些微生物在其群落内进行通信，并通过称为群体感应 (QS) 的分子系统来调节群体行为。在本研究中，我们旨在研究人工甜味剂对这种细菌通信系统的影响。使用生物传感器测定、生物物理蛋白质特性测定方法、微尺度热泳、群集运动测定、生长测定以及分子对接，我们表明阿斯巴甜、三氯蔗糖和糖精对革兰氏阴性菌 -酰基高丝氨酸内酯为基础的（AHL）通信系统具有显著的抑制作用。我们的研究表明，这三种人工甜味剂不是杀菌的。使用 LasR 作为 AHL 的代表性参与受体的蛋白 -配体对接和相互作用分析表明，人工甜味剂结合到蛋白质的配体结合口袋中，可能干扰天然配体的适当结合，从而阻碍蛋白质折叠。我们的研究结果表明，这些人工甜味剂可能通过 QS 抑制来影响肠道微生物群落的平衡。因此，我们推断这些人工甜味剂会对肠道微生物功能的核心的许多分子事件产生影响，进而对宿主代谢产生影响。
