Fasting-mimicking diet remodels gut microbiota and suppresses colorectal cancer progression

Fasting-mimicking diet (FMD) is a dietary intervention with reported benefits in cancer. In a colorectal cancer (CRC) mouse model, we evaluated a 4-day cyclic FMD using immune profiling, microbiota analysis, and anti-PD-1 treatment. FMD suppressed CRC growth, reduced proliferation and angiogenesis markers, and increased tumor-infiltrating lymphocytes, especially CD8+ T cells. FMD enriched protective gut microbiota, notably Lactobacillus. Oral supplementation with Lactobacillus johnsonii recapitulated FMD’s antitumor and immune effects, suppressing tumor growth and increasing CD45+ and CD8+ T cells. FMD combined with anti-PD-1 further inhibited CRC progression. These findings indicate L. johnsonii is necessary for FMD’s anticancer effects in CRC, acting via microbiota and immune modulation in mice.