Two promising new ways to prevent cholera are on the horizon. One is an entirely new kind of vaccine. The other is as simple as a cup of yogurt.

Both may offer fast, cheap protection from explosive outbreaks of a disease that claims tens of thousands of lives each year.

The research has so far only been done in animals. Human studies are yet to come. 

Cholera declawed

Cholera causes such serious diarrhea that it can kill within hours. Current vaccines take at least 10 days to work, don’t provide complete protection and don’t work well for young children. 

One group of scientists working to create a better vaccine engineered cholera bacteria that are missing the genes that make the microbe toxic. 

The researchers fed the modified bacteria to rabbits. The microbes colonized the animals’ guts but did not make them sick. 

When the scientists then fed rabbits normal, disease-causing cholera 24 hours later, most of the animals survived. 

Those that did get sick took longer to do so than rabbits given unmodified bacteria, or modified bacteria that had been killed. Those animals died within hours. 

The engineered cholera bacteria provided protection much faster than a conventional vaccine. They acted as a probiotic: colonized the animals’ intestines in less than a day and prevented the disease-causing microbes from getting a foothold. 

The researchers expect that the modified bacteria will also act like a typical vaccine, stimulating the body’s immune system to fight a future cholera infection. 

“This is a new type of therapy,” Harvard University Medical School microbiologist Matthew Waldor said. “It’s both a probiotic and a vaccine. We don’t know the right name for it yet.”

The research is published in the Science Translational Medicine journal. 

Yogurt solution

In another study in the same journal, a group of researchers discovered that a microbe commonly found in yogurt, cheese and other fermented dairy products can prevent cholera infection. 

Bioengineer Jim Collins at the Massachusetts Institute of Technology and colleagues had been working on genetically modifying the bacteria, known as Lactococcus lactis, to treat cholera. 

It hadn’t been working. 

But they accidentally discovered that unmodified L. lactis keeps cholera germs in check by producing acid that the disease-causing microbes can’t tolerate. 

Feeding mice doses of L. lactis bacteria every 10 hours nearly doubled their survival rate from cholera infection. 

“It was remarkably surprising and satisfying,” Colllins said. “We were really getting frustrated.” 

They also designed a strain of L. lactis that turns a cholera-infected mouse’s stool red. It could be a useful diagnostic, for example, to identify those carrying the bacteria but not showing symptoms. 

Collins said pills of L. lactis bacteria — or simply ample supplies of fermented milk products — could be “a very inexpensive, safe and easy-to-administer way to keep some of these outbreaks in check.”

Waldor said his group’s modified-cholera vaccine also could be grown and packaged in pills quickly and easily in case of an outbreak. 

Both caution that these animal studies are a long way from new treatments for human patients. They need to be proven in clinical trials. 

Beyond cholera

The two studies could not only have an impact on cholera, but could also influence how doctors treat other intestinal diseases and manage gut health, according to Robert Hall, who oversees research funded by the National Institute of Allergy and Infectious Diseases. 

While fermented foods promising better health are widely available, “the studies with probiotics in the field have really seldom shown great effectiveness when they’re done scientifically,” Hall said. 

The work Collins’s group did not only shows effectiveness, but explains how it works: by “making the intestine inhospitable” to cholera, he added.

Hall wrote a commentary accompanying the two studies. 

Other gut diseases work the same way as cholera, he noted, so it’s possible that other microbes could be developed that block harmful germs from gaining a foothold while acting as vaccines at the same time.

“It’s a very exciting principle,” Hall said. 

 
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