Sweetener saccharin shows surprising power against antibiotic resistance

Abstract

Artificial sweeteners like saccharin, commonly used as sugar substitutes, are revealing surprising capabilities in combating antibiotic-resistant bacteria. Recent research indicates that saccharin and similar compounds, such as acesulfame-K and sucralose, can inhibit the growth of multidrug-resistant pathogens like Acinetobacter baumannii and Pseudomonas aeruginosa. These sweeteners disrupt bacterial biofilm formation and motility, and they can enhance the effectiveness of existing antibiotics by increasing bacterial membrane permeability, leading to cell lysis. Notably, acesulfame-K demonstrated potent antimicrobial activity in ex vivo wound models, suggesting potential therapeutic applications.​

However, there's a complex side to this narrative. Studies have shown that artificial sweeteners can also promote the spread of antibiotic resistance genes. They do this by increasing bacterial cell membrane permeability and stimulating the expression of genes involved in DNA uptake, thereby facilitating horizontal gene transfer through natural transformation. Additionally, these sweeteners can induce oxidative stress in bacteria, further enhancing the conjugative transfer of resistance plasmids within gut microbiota. This dual role underscores the need for careful consideration in the use of artificial sweeteners, balancing their potential benefits in antimicrobial therapy against the risks of promoting antibiotic resistance. 

• PMID: 36524841
 
• PMCID: PMC9762752
 
• DOI: 10.1080/19490976.2022.2157698

Key References:

1. Yu Z, Wang Y, Henderson IR, Guo J. (2022). Artificial sweeteners stimulate horizontal transfer of extracellular antibiotic resistance genes through natural transformation. ISME J, 16(2), 543–554. doi:10.1038/s41396-021-01095-6 PMID: 34465899​

2. Yu Z, Henderson IR, Guo J. (2023). Non-caloric artificial sweeteners modulate conjugative transfer of multi-drug resistance plasmid in the gut microbiota. Gut Microbes, 15(1), 2157698. doi:10.1080/19490976.2022.2157698 PMID: 36524841​

3. Yang G, Cao JM, Cui HL, Zhan XM, Duan G, Zhu YG. (2023). Artificial Sweetener Enhances the Spread of Antibiotic Resistance Genes During Anaerobic Digestion. Environ Sci Technol, 57(30), 10919–10928. doi:10.1021/acs.est.2c08673 PMID: 37475130​

4. Zhang L, Huang Y, Wang Y, Yu Z, Guo J. (2022). Non-caloric artificial sweeteners exhibit antimicrobial activity against bacteria and promote bacterial evolution of antibiotic tolerance. Sci Total Environ, 826, 154213. doi:10.1016/j.jhazmat.2022.128840 PMID: 35398799

The Sweet Twist: How Saccharin and Other Sweeteners Are Shaping the Fight Against Superbugs

Impact of saccharin on cellular growth and morphology. 

Credit: EMBO Molecular Medicine (2025). DOI: 10.1038/s44321-025-00219-1

It turns out your favorite diet soda might be doing more than satisfying your sweet tooth—it could be playing a surprising role in modern medicine. Artificial sweeteners like saccharin, acesulfame-K, and sucralose—those tiny names on the back of your snack wrappers—are now being looked at as unlikely heroes in the battle against superbugs.

Could Sweeteners Be the Secret Weapon? In a twist that seems straight out of a sci-fi movie, recent research suggests these everyday sweeteners can actually slow down some of the most dangerous bacteria out there. We’re talking about stubborn hospital infections caused by bacteria like Acinetobacter baumannii and Pseudomonas aeruginosa. These bugs laugh in the face of many antibiotics, but sweeteners might just be their kryptonite. Scientists have found that these compounds mess with how the bacteria move, grow, and even defend themselves. In lab studies, acesulfame-K helped clean up infected wounds—impressive for something you’d usually find in a sugar packet.

But Here’s the Catch… Before we start stocking hospital shelves with sweetener packs, there’s a downside to consider. Some studies show that while these sweeteners can knock out bad bacteria, they might also help them share their resistance tricks with each other. Yep, they could actually make the enemy stronger by boosting the way bacteria exchange genetic material. In your gut, for example, these compounds could open the door for bacteria to trade secrets—specifically, resistance genes.

A Bittersweet Dilemma This makes things complicated. Sweeteners could offer a new, accessible way to fight infections. But if we’re not careful, we might also be supercharging the bugs we’re trying to beat. Scientists are working hard to untangle this double-edged sword.

So, the next time you tear open that sweetener packet, remember—there’s more to the story than calories. You might just be holding a new kind of medicine… or a microbial plot twist in the making.