Longevity Institute, School of Gerontology, Department of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA.
USC Dornsife College of Letters, Arts & Sciences, Department of Biological Sciences, University of Southern California, 3551 Trousdale Pkwy, Los Angeles, CA 90089-0191, USA.
Cell Rep. 2019 Mar 5;26(10):2704-2719.e6. doi: 10.1016/j.celrep.2019.02.019.
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.
饮食干预可能是治疗炎症性肠病(IBD)的有效方法。我们测试了为期 4 天的禁食模拟饮食(FMD)周期对慢性葡聚糖硫酸钠(DSS)诱导的小鼠模型的影响,该模型导致与 IBD 相关的症状和病理。这些 FMD 周期减少了肠道炎症,增加了干细胞数量,刺激了保护性肠道微生物群,并逆转了 DSS 引起的肠道病理学,而仅饮水的禁食增加了再生和减少了炎症标志物,而没有逆转病理学。来自 DSS 和 FMD 治疗小鼠的乳杆菌或粪便微生物群的移植逆转了 DSS 诱导的结肠缩短,减少了炎症,并增加了结肠干细胞。在一项临床试验中,三个 FMD 周期降低了与全身炎症相关的标志物。FMD 周期对肠道微生物群组成、免疫细胞谱、肠道干细胞水平以及逆转与 IBD 相关的病理学的影响,以及临床试验中显示的抗炎作用,表明 FMD 周期有望改善人类 IBD 相关炎症。