High-Protein Diets May Blunt Cholera Infection, Study Suggests

A diet rich in specific proteins such as casein could offer a low-cost, low-risk way to curb cholera infection, a new study suggests—a finding that may carry particular relevance for countries such as India, where the disease continues to surface in pockets with inadequate access to safe drinking water and sanitation.

Researchers from the University of California, Riverside (UCR) have found that diets high in casein—the main protein in milk and cheese—and wheat gluten significantly reduced the ability of Vibrio cholerae, the bacterium that causes cholera, to colonize the gut. The study, published in Cell Host and Microbe, shows that diet alone can dramatically alter the severity of infection.

“I wasn’t surprised that a diet could affect the health of someone infected with the bacteria. But the magnitude of the effect surprised me,” said Ansel Hsiao, associate professor of microbiology and plant pathology at UCR and the senior author of the study. “We saw up to 100-fold differences in the amount of cholera colonization as a function of diet alone.”

While prompt rehydration therapy is lifesaving, the disease can be fatal if untreated. Antibiotics may shorten the duration of illness but do not neutralize the toxins released by the bacteria.

The researchers set out to examine whether diet—known to strongly influence the gut microbiome—could also affect the behavior of invasive pathogens. In experiments conducted on infected mice, they compared diets high in protein, simple carbohydrates, and fat.

The results were striking. High-fat diets had little impact on the infection, and carbohydrate-rich diets showed only modest benefits. In contrast, diets rich in dairy protein and wheat gluten “virtually shut the pathogen out,” the researchers reported.

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

Further analysis revealed the biological mechanism behind this effect. The proteins appeared to suppress a syringe-like structure on the surface of the cholera bacterium known as the type 6 secretion system (T6SS). This structure allows the bacteria to inject toxins into neighboring cells and outcompete other microbes in the gut. When T6SS activity is muted, Vibrio cholerae struggles to establish itself.

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

The study, titled Diet Modulates Vibrio Cholerae Colonization and Competitive Outcomes with the Gut Microbiota, was co-authored by Rui Liu, Yue Zhang, Siyi Ge, Jennifer Y. Cho, Nathaniel C. Esteves, and Jun Zhu.

Although the research was conducted in mice, the authors believe the findings may translate to humans. Dr. Hsiao said future work would focus on testing the impact of high-protein diets on human microbiomes, as well as examining whether similar dietary approaches could limit 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,” he said. “The more we can improve peoples’ diets, the more we may be able to protect people from succumbing to disease.”