By Morgan Nwanguma
A newly developed antibiotic known as EVG7 may offer a highly effective way to combat Clostridioides difficile, a dangerous gut bacterium that frequently recurs after treatment. In mouse studies, researchers found that even very low doses of EVG7 successfully cleared the infection and helped prevent it from returning. Unlike many existing antibiotics that disrupt large portions of the gut microbiome, EVG7 appears to preserve beneficial bacteria that naturally keep C. difficile under control.
Scientists in Leiden reported that EVG7 can target C. difficile efficiently with minimal dosing, significantly lowering the risk of relapse – a persistent challenge with current treatments. The findings were published in the journal Nature Communications.
C. difficile is a resilient intestinal bacterium that can cause severe illness, particularly in older adults and individuals with weakened immune systems. It produces toxins that lead to intense diarrhea and inflammation of the gut. While antibiotics remain the standard treatment, many patients suffer repeated infections after initial recovery.
The experimental drug was developed by researchers in the group of Professor Nathaniel Martin at the Institute of Biology Leiden (IBL). EVG7 is designed as a more potent and targeted version of the commonly used antibiotic vancomycin, aiming to improve treatment outcomes while reducing harm to the gut’s natural microbial balance.
“With existing antibiotics, C. difficile sometimes reappears just weeks after treatment,” says researcher and lead author Elma Mons. Part of the reason is that the bacterium produces spores that can survive treatment and later develop into new bacteria, allowing the infection to return.
Low-Dose Antibiotic Delivers Strong Results
Mons and her colleagues investigated how EVG7 performs against C. difficile infections in mice. Given its higher potency compared to vancomycin, the drug was tested at a much lower dose. The results were striking: mice treated with a low dose of EVG7 were far less likely to experience a relapse.
Other treatment approaches proved less effective. A reduced dose of vancomycin did not prevent recurrence, while a higher dose of EVG7 also yielded weaker outcomes. Overall, the findings showed that a low dose of EVG7 provided the most effective protection.
Preserving the Gut Microbiome
To understand why the lower dose worked best, the researchers examined the gut microbiome of the treated mice – the community of bacteria that naturally inhabits the intestines. They found that mice given a small dose of EVG7 retained significantly more beneficial bacteria, particularly members of the Lachnospiraceae family.
“Those bacteria actually protect against C. difficile,” says Mons.
In contrast, a lot of current antibiotics eliminate large portions of the microbiome, including beneficial microbes that play a key role in maintaining gut health. EVG7, however, appears to preserve most of these protective bacteria. By remaining intact, these microbes can prevent residual spores from developing into harmful C. difficile cells and causing a recurrence of the infection. ‘That approach fits a growing trend among doctors to preserve the microbiome as much as possible,’ Mons explains
Lesser Threat of Antibiotic Resistance
By means of smaller antibiotic doses can occasionally heighten concerns regarding antibiotic resistance. “That happens when you don’t completely kill the bacteria but merely irritate them,” Mons says. “They can then come back stronger.”
According to the scientists, EVG7 does not seem to share this limitation. Even at low doses, the drug remains potent enough to effectively clear C. difficile, and early evidence suggests it may be less likely to promote antibiotic resistance.
Next Steps Toward Human Trials
Mons expressed hope that additional funding will allow the research to progress. Before EVG7 can be tested in humans, it must first undergo toxicity studies to confirm its safety. If those results are positive, clinical trials could begin within the next few years.
“But that means finding investors,” she adds. “For antibiotics, that’s not easy. Pharmaceutical companies make far less profit on them than on, say, cancer drugs, so interest is limited.”
In spite of these challenges, scientists believe EVG7 could sooner or later become a foremost treatment for C. difficile infections. “If a patient relapses and needs another hospital admission, that’s costly too,” Mons points out.
The study, titled “Experimental glycopeptide antibiotic EVG7 prevents recurrent Clostridioides difficile infection by sparing members of the Lachnospiraceae family,” was published in Nature Communications. The research was conducted in collaboration with the teams of Wiep Klaas Smits at Leiden University Medical Center and Casey Theriot at North Carolina State University.
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