A high-protein diet can defeat cholera infection, claims research

Cholera, a severe bacterial infection that causes diarrhea and kills if untreated, can be defeated with a diet high in protein, according to a new study from UC Riverside.

Specifically, the study found that diets high in casein, the main protein in milk and cheese, as well as wheat gluten, could make a dramatic difference in the amount of cholera bacteria able to infect the gut.

“I wasn’t surprised that diet could affect the health of someone infected with the bacteria. But the magnitude of the effect surprised me,” said Ansel Hsiao, UCR associate professor of microbiology and plant pathology and senior author of the study published in Cell Host and Microbe.

“We saw up to 100-fold differences in the amount of cholera colonization as a function of diet alone,” Hsiao said.

Knowing that food has a strong effect on the community of bacteria and other microbes naturally living in the gut, the researchers initially set out to understand whether infectious, invasive microbes would be similarly affected by diet.

The researchers tested diets high in protein, high in simple carbohydrates, and high in fat on cholera’s ability to colonize the gut of an infected mouse. High-fat diets did little to slow the infection, and carbohydrates showed limited effects. But the dairy and wheat gluten diets virtually shut the pathogen out.

“The high-protein diet had one of the strongest anti-cholera effects compared to a balanced diet. And not all proteins are the same,” Hsiao said. “Casein and wheat gluten were the two clear winners.”

Looking more deeply into these results, the researchers found the proteins suppress a microscopic syringe-like structure on the surface of cholera bacteria used for injecting toxins into neighboring cells. When this structure, called the type 6 secretion system, or T6SS, is muted, cholera has a difficult time killing other bacteria and taking up space in the gut.

Cholera remains a public health threat in parts of Asia and Sub-Saharan Africa with limited clean water access. Treatment typically focuses on rehydration. Antibiotics can shorten the illness, but they don’t neutralize the toxins cholera leaves behind.

Overuse of antibiotics also carries the risk of creating bacteria that no longer respond to drugs. Though antibiotic-resistant cholera is not an imminent threat, the quick-to-adapt nature of bacteria means a drug could quickly and sometimes unexpectedly change cholera’s behavior.

“Dietary strategies won’t generate antibiotic resistance in the same way a drug might,” Hsiao said.

For now, dietary strategies could offer a low-cost, low-risk tool to reduce the severity or likelihood of infection in vulnerable human populations.

“Wheat gluten and casein are recognized as safe in a way a microbe is not, in a regulatory sense, so this is an easier way to protect public health,” Hsiao said.

And although these findings come from mice, Hsiao expects high-protein diets would have similar effects for humans, so he would like to test these results on human microbiomes in the future, as well as on other infectious bacteria.

“Some diets will be more successful than others, but if you try this for pathogens other than cholera, I suspect we’ll also see a beneficial effect,” Hsiao said. “The more we can improve peoples’ diets, the more we may be able to protect people from succumbing to disease.”

Reference:

Rui Liu, Yue Zhang, Diet modulates Vibrio cholerae colonization and competitive outcomes with the gut microbiota, Cell Host & Microbe, DOI:10.1016/j.chom.2025.11.004