Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota.
Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota.
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DOI：
10.1016/j.cmet.2018.05.006
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发表时间：
2018-06-05
期刊：
影响因子：
29
通讯作者：
Piccio L
中科院分区：
文献类型：
--
作者：
Cignarella F;Cantoni C;Ghezzi L;Salter A;Dorsett Y;Chen L;Phillips D;Weinstock GM;Fontana L;Cross AH;Zhou Y;Piccio L
多发性硬化症（MS）是一种中枢神经系统（CNS）炎性脱髓鞘疾病，受遗传和环境因素的相互作用影响。据推测是自身免疫性疾病。MS在西方国家更常见，饮食差异可能导致其特定的地理分布。有关饮食与MS的研究尚未得出结论。饮食可以影响免疫反应的一种机制是肠道微生物组，它正在成为许多人类疾病的关键因素。在这里，我们表明，间歇性禁食（IF）改善MS动物模型，实验性自身免疫性脑脊髓炎（EAE）的临床过程和病理，导致炎症，脱髓鞘和轴突损伤较少。IF改变了肠道微生物组，导致细菌丰富度增加以及乳杆菌科、拟杆菌科和普雷沃氏菌科的富集。肠道微生物丰富度与瘦素水平呈负相关。微生物代谢途径分析显示，IF诱导的肠道微生物组变化增加了酮的形成和谷胱甘肽代谢，增强了抗氧化途径。此外，IF对肠道固有层中T细胞的组成有直接影响，产生IL-17的T细胞减少，调节性T细胞数量增加。这些作用可能调节全身免疫反应。重要的是，来自IF小鼠的粪便微生物组移植改善了正常饮食的免疫受体小鼠的EAE，表明IF免疫调节作用至少部分由肠道植物群介导。我们将我们的研究结果转化为MS患者在MS患者复发的试点临床试验，以测试IF对临床和实验室指标的安全性，可行性和影响。观察到对几种免疫炎症参数水平以及肠道植物群的潜在有益作用，类似于在EAE小鼠中观察到的保护性变化。总之，IF具有至少部分由肠道微生物组介导的强效免疫调节作用。间歇性禁食（IF）通过对肠道微生物群的影响在多发性硬化症动物模型中提供保护，在经历短期IF的复发性MS患者中观察到肠道微生物群的类似变化。
Multiple sclerosis (MS) is a central nervous system (CNS) inflammatory demyelinating disease impacted by the interplay of genetic and environmental factors. It is presumed to be autoimmune. MS is more common in western countries and differences in diet could contribute to its particular geographical distribution. Studies relating diet to MS have been inconclusive. A mechanism through which diet can influence immune responses is the gut microbiome, which is emerging as a critical contributor in numerous human diseases. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS animal model, experimental autoimmune encephalomyelitis (EAE), leading to less inflammation, demyelination and axonal damage. IF changed the gut microbiome resulting in increased bacteria richness and enrichment of the Lactobacillaceae, Bacterioidaceae and Prevotellaceae families. Gut microbiome richness was inversely correlated with leptin levels. Microbial metabolic pathway analysis revealed that IF-induced changes to the gut microbiome increased ketone formation and glutathione metabolism, enhancing anti-oxidative pathways. Furthermore, IF had direct effects on the composition of T cells in the gut lamina propria with a reduction of IL-17 producing T cells and an increase in the number of regulatory T cells. These effects might modulate systemic immune responses. Importantly, fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF immunomodulatory effects are at least partially mediated by the gut flora. We translated our findings to MS patients in a pilot clinical trial in MS patients undergoing relapse to test the safety, feasibility and effects of IF on clinical and laboratory measures. Potentially beneficial effects on levels of several immune inflammatory parameters as well as gut flora that resembled the protective changes observed in mice in EAE were observed. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome. Intermittent fasting (IF) confers protection in the multiple sclerosis animal model through effects on the gut microbiota, with similar changes to gut microbiota observed in relapsing MS patients undergoing short-term IF.
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影响因子：
4.4
作者：
Fettweis JM;Serrano MG;Sheth NU;Mayer CM;Glascock AL;Brooks JP;Jefferson KK;Vaginal Microbiome Consortium (additional members);Buck GA
通讯作者：
Buck GA
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
11.2
作者：
Arumugam, Thiruma V.;Phillips, Terry M.;Cheng, Aiwu;Morrell, Christopher H.;Mattson, Mark P.;Wan, Ruiqian
通讯作者：
Wan, Ruiqian
影响因子：
14.5
作者：
Cutter, GR;Baier, ML;Willoughby, E
通讯作者：
Willoughby, E
影响因子：
5.8
作者：
Fischer, JS;Rudick, RA;Reingold, SC
通讯作者：
Reingold, SC