Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome.
Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome.
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生酮饮食通过改变肠道微生物组减少结肠第 3 组先天淋巴细胞来缓解结肠炎
DOI：
10.1038/s41392-021-00549-9
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发表时间：
2021-04-23
影响因子：
39.3
通讯作者：
Ma Y
中科院分区：
文献类型：
--
作者：
Kong C;Yan X;Liu Y;Huang L;Zhu Y;He J;Gao R;Kalady MF;Goel A;Qin H;Ma Y
越来越多的证据表明，生酮饮食（KD）介导循环酮体的升高，并发挥潜在的抗炎作用;然而，这种独特的饮食对结肠炎的影响仍然未知。我们使用葡聚糖硫酸钠（DSS）炎症性结肠炎动物模型进行了一系列系统研究。动物喂食KD、低碳水化合物饮食（LCD）或正常饮食（ND）。在验证实验中使用无菌小鼠。通过转录组测序、RT 2 profiler PCR阵列、组织病理学和免疫荧光分析结肠组织。采用代谢分析试剂盒分析血清样品。粪便样品通过16 S rRNA基因测序、液相色谱-质谱和气相色谱-质谱进行分析。我们观察到KD通过以不同于LCD的方式改变肠道微生物群和代谢物来减轻结肠炎。定量饮食实验证实了KD相对于LCD的独特影响，在阿克曼氏菌中可重复增加，而在埃希氏菌/志贺氏菌中观察到相反的情况。在结肠炎诱导后，KD保护肠屏障功能，并减少RORγt+ CD 3 − 3组先天性淋巴细胞（ILC 3）和相关炎症细胞因子（IL-17α，IL-18，IL-22，Ccl 4）的产生。最后，将粪便微生物群移植到无菌小鼠中揭示了KD介导的结肠炎抑制和ILC 3调节依赖于肠道微生物群的修饰。总之，我们的研究提出了KD结肠炎治疗期间发生的微生物组-代谢组学变化的全球观点，并将肠道微生物组和ILC 3的调节确定为IBD饮食治疗的新靶点。
Accumulating evidence suggests that ketogenic diets (KDs) mediate the rise of circulating ketone bodies and exert a potential anti-inflammatory effect; however, the consequences of this unique diet on colitis remain unknown. We performed a series of systematic studies using a dextran sulfate sodium (DSS) animal model of inflammatory colitis. Animals were fed with a KD, low-carbohydrate diet (LCD), or normal diet (ND). Germ-free mice were utilized in validation experiments. Colon tissues were analyzed by transcriptome sequencing, RT2 profiler PCR array, histopathology, and immunofluorescence. Serum samples were analyzed by metabolic assay kit. Fecal samples were analyzed by 16S rRNA gene sequencing, liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry. We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD. Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase inAkkermansia, whereas the opposite was observed forEscherichia/Shigella. After colitis induction, the KD protected intestinal barrier function, and reduced the production of RORγt+CD3−group 3 innate lymphoid cells (ILC3s) and related inflammatory cytokines (IL-17α, IL-18, IL-22, Ccl4). Finally, fecal microbiota transplantation into germ-free mice revealed that the KD- mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota. Taken together, our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment, and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.
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影响因子：
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