Artificial Sweeteners May Contribute to Antibiotic Resistance through Horizontal Gene Transfer

by | Apr 28, 2021 | 2021, Digestive Health, Sweeteners

Written by Joyce Smith, BS. This study demonstrates that commonly used nonnutritive sweeteners have the ability to promote the spread of antibiotic-resistant genes in the intestine.

MIcrobiome - probioticsAntimicrobial resistance (AMR), one of the greatest human health threats today 1, is responsible for approximately 700,000 deaths annually worldwide 2  and unless curtailed, the misuse or overuse of antibiotics 3 and the consequential AMR will contribute to an estimated death of 10 million people2.  The emergence of antibiotic resistant genes (ARG) is driven by a process called horizontal gene transfer (HGT). Conjugation is a significant HGT mechanism which promotes ARGs by transferring mobile genetic material from one bacteria to another 4. The study team describes this process as the “bacterial equivalent of sexual reproduction or mating and occurs when two bacteria come into direct contact during which the resistance genes are transferred from the donor to the recipient”, and as result, the recipient might become a multi-drug resistant strain of bacteria.

Nonnutritive sweeteners, approved by the U.S. Food and Drug Administration (FDA), boast a global consumption of approximately 117,000 metric tons annually 5. They travel unmetabolized through the digestive tract 6 to be excreted intact into the environment  where they can be detected in ground water and  wastewater treatment plants (WWTPs) 7. Although they have been developed and promoted as safe food additives that reduce sugar consumption, some commonly used sweeteners have recently been associated with health risks. Saccharin (SAC), sucralose (SUC), and aspartame (ASP) contribute to urinary bladder tumors 8 and glucose intolerance, that has been thought to occur through alterations in the gut microbiota 9. Studies have also provided evidence that SAC, SUC, and ASP, as well as acesulfame potassium (ACE-K), can cause DNA damage in bacteria 10, and lead to conjugative ARG transfer. Recent studies have also demonstrated that consumption of SAC, SUC, and ASP is associated with shifts in the gut microbiota that are similar those caused by antibiotics.

Yu and colleagues hypothesize 11 that just as antibiotics can promote the spread of ARGs, nonnutritive sweeteners may enhance the horizontal transfer of ARGs. The team used three model conjugation systems to investigate whether SAC, SUC, ASP, and ACE-K promote plasmid-mediated conjugative transfer in both environmental and clinical settings. They were also able to visualize the conjugation process at the single-cell level using microfluidics and confocal microscopy. Their final endeavor included a whole-genome RNA sequencing analysis and measurement of changes in reactive oxygen species (ROS) production, the SOS response (an error-prone repair system that contributes significantly to DNA changes and mutagenesis), and cell membrane permeability.

They found that all four sweeteners, SAC, SUC, ASP, and ACE-K, promoted HGT between the same bacteria and different phylogenetic strains (pathogenic and nonpathogenic) in both environmental and clinical settings via plasmid-mediated conjugative transfer. During the gene transfer from donor to recipient bacteria, researchers saw an increase in ROS production, SOS response, and increased cell membrane permeability. These results provide insight into the spread of antimicrobial resistance and point to the potential risk associated with the presence of these sweeteners in food and beverages. These results should be a wake-up call for more research that further explores the potential contribution of nonnutritive sweeteners to antibiotic resistance.

Source: Yu, Zhigang, Yue Wang, Ji Lu, Philip L. Bond, and Jianhua Guo. “Nonnutritive sweeteners can promote the dissemination of antibiotic resistance through conjugative gene transfer.” The ISME Journal (2021): 1-14.

© The Author(s) 2021. This article is published with open access

Click here to read the full text study.

Posted April 28, 2021.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

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