Inhibitory Effects of Artificial Sweeteners on Bacterial Quorum Sensing

Int J Mol Sci. 2021 Sep 13;22(18):9863. doi: 10.3390/ijms22189863.

Abstract

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 N-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.

Keywords: artificial sweeteners; dysbiosis; gut microbiota; normobiosis; quorum sensing.

MeSH terms

  • Aspartame / adverse effects
  • Bacterial Proteins / genetics*
  • Biosensing Techniques / methods
  • Carboxylic Ester Hydrolases / genetics
  • Cell Communication / drug effects
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / genetics
  • Gram-Negative Bacteria / drug effects
  • Humans
  • Molecular Docking Simulation
  • Quorum Sensing / drug effects*
  • Saccharin / adverse effects
  • Sucrose / adverse effects
  • Sucrose / analogs & derivatives
  • Sweetening Agents / adverse effects*
  • Sweetening Agents / pharmacology
  • Trans-Activators / genetics*

Substances

  • Bacterial Proteins
  • LasR protein, Pseudomonas aeruginosa
  • Sweetening Agents
  • Trans-Activators
  • Sucrose
  • trichlorosucrose
  • Carboxylic Ester Hydrolases
  • N-acyl homoserine lactonase
  • Saccharin
  • Aspartame