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Cell Rep. 2019 Mar 5;26(10):2704-2719.e6. doi: 10.1016/j.celrep.2019.02.019.

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

Author information

1
Longevity Institute, School of Gerontology, Department of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA.
2
USC Dornsife College of Letters, Arts & Sciences, Department of Biological Sciences, University of Southern California, 3551 Trousdale Pkwy, Los Angeles, CA 90089-0191, USA.
3
USC Dornsife College of Letters, Arts & Sciences, Department of Biological Sciences, University of Southern California, 3551 Trousdale Pkwy, Los Angeles, CA 90089-0191, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, 1425 San Pablo St, Los Angeles, CA 90033, USA; IFOM FIRC Institute of Molecular Oncology, Via Adamello 16, Milano 20139, Italy. Electronic address: vlongo@usc.edu.

Abstract

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.

KEYWORDS:

Crohn’s disease; fasting; fasting-mimicking diet; gut microbiota; inflammation; inflammatory bowel disease; intermittent fasting; microbiome; ulcerative colitis

PMID:
30840892
DOI:
10.1016/j.celrep.2019.02.019
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