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Australian researchers conducted a study showing that commonly used non-nutrient sweeteners can promote the spread of antibiotic-resistant genes in the gut.
The study found that the sweeteners saccharin, sucralose, aspartame, and acesulfame potassium all promoted horizontal gene transfer between bacteria in environmental and clinical settings.
Sweeteners accelerated the exchange of antibiotic resistance (ARG) genes through a process called conjugation. Genes are transferred from a donor bacteria to a recipient bacteria, which can then develop multidrug resistance, explains Zhigang Yu and colleagues at the University of Queensland in St. Lucia, Brisbane.
Write in Journalism, the team says the findings provide insight into the spread of antimicrobial resistance and highlight the potential risk associated with the presence of these sweeteners in foods and drinks.
Antimicrobial resistance is one of the world’s biggest threats
Antimicrobial resistance (AMR) represents one of the most significant global threats to public health and biosecurity in the decades to come.
Currently, 700,000 people worldwide die each year from infections caused by bacteria resistant to antibiotics. It is estimated that 10 million people will die from such infections by 2050 if action is not taken immediately.
The emergence of ARGs that give rise to resistant bacteria is generally attributed to the misuse or overuse of antibiotics.
The spread of ARGs among different bacterial species is mainly due to a process called horizontal gene transfer (HGT). Conjugation is a mechanism of HGT that transfers the ARGs transported to mobile genetic elements such as plasmids from one bacterial cell to another. ARGs are transferred via a pilus or porous channel connecting the host and the recipient bacteria.
Where do sweeteners come from?
Although non-nutritious sweeteners have been developed and promoted as safe food additives that allow individuals to avoid the ill effects of consuming sugar, some commonly used sweeteners have recently been associated with health risks.
For example, in vitro studies have shown that the sweeteners saccharin (SAC), sucralose (SUC) and aspartame (ASP) can induce the formation of bladder tumors.
These sweeteners are also associated with an intolerance to glucose, which would come from alterations of the intestinal microbiota.
Studies have also provided evidence that SAC, SUC and ASP, as well as acesulfame potassium (ACE-K), cause DNA damage in bacteria. Researchers say this is likely to activate the DNA damage response system (SOS response).
Additionally, evidence suggests that conjugative ARG transfer may be related to the SOS response.
Studies have also recently shown that the use of SAC, SUC and ASP is associated with changes in the gut microbiota that resemble those caused by antibiotics.
“Since antibiotics can promote the spread of ARGs, we hypothesize that these non-nutritive sweeteners might have a similar effect,” Yu and the team wrote.
What did the researchers do?
The team used three models of conjugation systems to determine whether SAC, SUC, ASP, and ACE-K promote plasmid-mediated conjugative transfer in environmental and clinical settings.
The conjugation process was also visualized at the single cell level using microfluidics and confocal microscopy.
The researchers performed a whole genome RNA sequencing analysis and measured changes in reactive oxygen species (ROS) production, SOS response, and cell membrane permeability.
What did they find?
All four sweeteners were found to promote plasmid-mediated conjugative transfer between the same bacteria and different phylogenetic strains.
Bacteria exposed to these compounds exhibited increases in ROS production, SOS response, and conjugative ARG gene transfer at environmentally and clinically relevant concentrations.
The permeability of the cell membrane, especially that of the donor, also played an important role in the frequency of conjugative transfer.
When the cell permeability of the donor (but not of the recipient bacteria) was increased, a significant increase in conjugative transfer was observed. When the cell permeability of the recipient (but not the donor) was increased, no significant change in conjugative transfer was observed.
“It has been reported that in the transfer of ARGs, donors with high expression of the conjugation machinery have been shown to be associated with recipients with low receptivity,” explains Yu and colleagues. “Thus, the increased patency of the donor can lead to an increase in the transfer of ARG to the recipient and lead to an increase in the frequency of conjugative transfer.”
What are the implications of the study?
Researchers say studies have previously shown that sewage treatment plants (WWTPs) can serve as hot spots for antibiotic-resistant bacteria and ARGs due to HGT among native bacterial species.
Given that the concentrations of non-nutritive sweeteners used in this study were relevant to the environment, it is reasonable to assume that upon exposure to these compounds, the frequency of transfer of ARGs would be favored in wastewater treatment plants. , indicates the team.
“It is possible that these sweeteners can cause a cascade of ARGs in wastewater treatment plants, thereby facilitating the increased development of antibiotic resistance in downstream environmental bacteria,” writes Yu and colleagues.
“Given the substantial application of these sweeteners in the food industry (over 117,000 metric tons consumed worldwide per year), our results are a red flag to begin to assess the potential roles of antibiotic type induced by non-nutritive sweeteners, ”the team concludes.
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