Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children.
Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children.
复制标题
肠道菌群的饮食调节有助于减轻儿童遗传性肥胖和单纯性肥胖
DOI：
10.1016/j.ebiom.2015.07.007
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发表时间：
2015-08
期刊：
影响因子：
11.1
通讯作者：
Zhao L
中科院分区：
文献类型：
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作者：
Zhang C;Yin A;Li H;Wang R;Wu G;Shen J;Zhang M;Wang L;Hou Y;Ouyang H;Zhang Y;Zheng Y;Wang J;Lv X;Wang Y;Zhang F;Zeng B;Li W;Yan F;Zhao Y;Pang X;Zhang X;Fu H;Chen F;Zhao N;Hamaker BR;Bridgewater LC;Weinkove D;Clement K;Dore J;Holmes E;Xiao H;Zhao G;Yang S;Bork P;Nicholson JK;Wei H;Tang H;Zhang X;Zhao L
肠道微生物群被认为是饮食相关肥胖的关键因素；然而，它在人类遗传性肥胖症（例如普瑞德威利综合征（PWS））的疾病表型发展中的作用仍然难以捉摸。在这项针对 PWS（n = 17）和单纯性肥胖（n = 21）儿童的住院干预试验中，富含不易消化碳水化合物的饮食可导致体重显着减轻，并伴随肠道微生物群的结构变化，同时减少血清抗原负荷并减轻炎症。对直接从宏基因组数据集组装的 161 个流行细菌基因组草图进行的共丰度网络分析显示，碳水化合物发酵产生乙酸的功能基因组组相对增加。基于 NMR 的尿液代谢组学分析显示饮食诱导的宿主代谢型总体变化，并发现三甲胺 N-氧化物和硫酸吲哚酚显着减少，这些宿主细菌共代谢物已知会导致代谢恶化。与这些有害共代谢物的尿液水平相关的特定细菌基因组被发现编码酶基因，通过肠道中胆碱或色氨酸的发酵产生其前体。当移植到无菌小鼠体内时，与来自同一志愿者的干预后微生物群相比，干预前的肠道微生物群诱导了更高的炎症和更大的脂肪细胞。我们基于多组学的系统分析表明，肠道菌群失调对儿童遗传性肥胖和单纯性肥胖具有显着的病因学贡献，这意味着潜在的有效缓解目标。饮食管理不善和基因突变是肥胖相关疾病毁灭性流行背后的两个主要驱动力。对驱动力和疾病终点之间因果关系的分子链缺乏了解会阻碍疾病预防和治疗的进展。我们发现，患有普瑞德威利综合征的遗传性肥胖儿童的肠道菌群与饮食相关肥胖儿童有着相似的失调现象。富含不可消化但可发酵碳水化合物的饮食可显着促进有益细菌群的生长并减少毒素产生者，这有助于缓解肥胖症的代谢恶化，无论主要驱动力如何。儿童遗传性肥胖和单纯性肥胖具有相似的失调肠道微生物群。富含不易消化的碳水化合物的饮食可显着改善肠道微生物群，并减轻遗传性肥胖和单纯性肥胖。确定了产生肥胖相关代谢物的特定细菌基因组。
Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader–Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation. Poorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found that children genetically obese with Prader–Willi syndrome shared a similar dysbiosis in their gut microbiota with those having diet-related obesity. A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces. Genetic and simple obesity in children shared a similar dysbiotic gut microbiota. A diet rich in non-digestible carbohydrates significantly improved gut microbiota and alleviated genetic and simple obesity. Specific bacterial genomes for producing obesity-related metabolites were identified.