Dietary-protein sources modulate host susceptibility to Clostridioides difficile infection through the gut microbiota

Clostridioides difficile causes nosocomial antibiotic-associated diarrhea on a global scale. Susceptibility to C. difficile infection (CDI) is influenced by the composition and metabolism of gut microbiota, which in turn are affected by diet. However, the mechanism underlying the interplay between diet and gut microbiota that modulates susceptibility to CDI remains unclear. Here, we show that a soy protein diet increases the mortality of antibiotic-treated, C. difficile-infected mice while also enhancing the intestinal levels of amino acids (aas) and relative abundance of Lactobacillus genus. Indeed, Ligilactobacillus murinus-mediated fermentation of soy protein results in the generation of aas, thereby promoting C. difficile growth, and the process involves the anchored cell wall proteinase PrtP. Thus, mutual interaction between dietary protein and the gut microbiota is a critical factor affecting host susceptibility to CDI, suggesting that dietary protein sources can be an important determinant in controlling the disease.

Automated summary

A soy protein diet increases the mortality rate of antibiotic-treated, C. difficile-infected mice and enhances the levels of amino acids and abundance of Lactobacillus genus in the intestines. The fermentation of soy protein by Ligilactobacillus murinus generates amino acids that promote the growth of C. difficile, and this process involves the anchored cell wall proteinase PrtP. Thus, the interaction between dietary protein and the gut microbiota is a critical factor affecting host susceptibility to CDI, suggesting that dietary protein sources play an important role in controlling the disease.