Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology

Abstract

Summary: Dietary interventions are potentially effective therapies for inflammatory bowel diseases (IBDs). We tested the effect of 4-day fasting-mimicking diet (FMD) cycles on a chronic dextran sodium sulfate (DSS)-induced murine model resulting in symptoms and pathology associated with IBD. These FMD cycles reduced intestinal inflammation, increased stem cell number, stimulated protective gut microbiota, and reversed intestinal pathology caused by DSS, whereas water-only fasting increased regenerative and reduced inflammatory markers without reversing pathology. Transplants of Lactobacillus or fecal microbiota from DSS- and FMD-treated mice reversed DSS-induced colon shortening, reduced inflammation, and increased colonic stem cells. In a clinical trial, three FMD cycles reduced markers associated with systemic inflammation. The effect of FMD cycles on microbiota composition, immune cell profile, intestinal stem cell levels and the reversal of pathology associated with IBD in mice, and the anti-inflammatory effects demonstrated in a clinical trial show promise for FMD cycles to ameliorate IBD-associated inflammation in humans. : Rangan et al. show that cycles of a fasting-mimicking diet (FMD) ameliorate intestinal inflammation, promote intestinal regeneration, and stimulate the growth of protective gut microbial populations in a mouse model displaying symptoms and pathology associated with IBD. They also show that a similar FMD is safe, feasible, and effective in reducing systemic inflammation and the consequent high levels of immune cells in humans. Keywords: fasting-mimicking diet, gut microbiota, microbiome, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, inflammation, fasting, intermittent fasting