Dietary protein as a regulator of colitis and colorectal cancer

Diet impacts the pathogenesis of gastrointestinal diseases including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Although dietary protein can influence physiologic health, its impact on these diseases has not been adequately investigated. Consequently, clinical guidelines on optimal protein intake (i.e. amount and source) to help prevent or treat these conditions are limited.

Recent preclinical and clinical studies have examined how modifying dietary protein can impact the pathogenesis of intestinal inflammation. For example, work in mice reveals that higher protein intake worsens colitis and that different dietary protein sources can exert differential effects on colitis severity. Microbial populations and their metabolism were shown to play an important role in mediating these effects. Studies in humans have shown that high intake of red meat is associated with increased IBD incidence and decreased time to relapse in patients with ulcerative colitis; however, it is unclear which other protein sources may be more beneficial. Although a direct connection between dietary protein and CRC has not been established, multiple preclinical studies have shown that reducing dietary protein exerts anticancer effects, including improved response to therapy across multiple tumor types. These effects were shown to be predominantly mediated by restricting tumors of exogenous growth-promoting amino acids, resulting in tumor stress, and in certain cases, activation of antitumor immunity.

As a result of multiple studies, we have gained important insights into the role of dietary protein in mediating colonic inflammation and cancer. This work motivates clinical studies to directly test whether modifying source or amount of protein intake in patients with IBD or CRC will be beneficial for reducing disease severity and improving response to therapy.