The study found that diets rich in casein, the primary protein found in milk and cheese, along with wheat gluten, greatly reduced how much cholera bacteria could colonize 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.

Testing Different Diets on Cholera Infection

Scientists have long known that diet shapes the community of microbes living in the gut. In this study, researchers wanted to see whether harmful, disease-causing bacteria would also respond to dietary changes.

To test this, they fed infected mice different diets. Some were high in protein, others high in simple carbohydrates, and others high in fat. The results were striking. High-fat diets had little impact on the infection, and carbohydrate-heavy diets offered only modest benefits. In contrast, diets rich in dairy proteins and wheat gluten almost completely prevented the bacteria from establishing itself in the gut.

“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.”

How Protein Disarms Cholera Bacteria

Further investigation revealed why these proteins were so effective. They interfere with a tiny, syringe-like structure on the surface of cholera bacteria that is used to inject toxins into nearby cells. This structure, known as the type 6 secretion system, or T6SS, helps the bacteria compete with other microbes and dominate the gut.

When this system is suppressed, cholera struggles to kill competing bacteria and cannot easily take over the intestinal environment.

A Potential Low-Cost Alternative to Antibiotics

Cholera remains a serious public health concern in regions with limited access to clean water, particularly in parts of Asia and Sub-Saharan Africa. Standard treatment focuses on rehydration, while antibiotics can shorten the illness but do not eliminate the toxins left behind.

There is also concern about the overuse of antibiotics, which can lead to drug-resistant bacteria. While antibiotic-resistant cholera is not currently widespread, bacteria can adapt quickly, and treatments may become less effective over time.

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

Because of this, dietary approaches could provide a safer and more affordable way to reduce the severity or likelihood of infection, especially in vulnerable 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.

What This Means for Humans

Although the findings are based on mouse studies, researchers believe similar effects could occur in humans. Hsiao plans to explore how these dietary changes influence the human gut microbiome and whether they could also help defend against 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.”