Depletion of Blautia Species in the Microbiota of Obese Children Relates to Intestinal Inflammation and Metabolic Phenotype Worsening
Depletion of Blautia Species in the Microbiota of Obese Children Relates to Intestinal Inflammation and Metabolic Phenotype Worsening
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DOI：
10.1128/msystems.00857-19
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发表时间：
2020-03-01
期刊：
影响因子：
6.4
通讯作者：
Sanz, Yolanda
中科院分区：
文献类型：
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作者：
Benitez-Paez, Alfonso;Gomez del Pugar, Eva M.;Sanz, Yolanda
对肥胖和对照组进行的横断面研究表明，肠道微生物群改变与肥胖之间存在关联，但与特定疾病表型的联系和因果关系的证据仍然很少。本研究旨在分析患有和不患有胰岛素抵抗的瘦弱和肥胖儿童的肠道微生物群，以表征与特定肥胖相关并发症的关联，并了解其在代谢性炎症中的作用。通过对16S rRNA基因扩增子进行大规模测序，并使用一种新的排列方法进行数据分析，我们发现肥胖儿童肠道微生物群中Blautia的发病率下降，尤其是Blautia luti和Blautia wexlerae，这在肥胖和胰岛素抵抗的情况下更为明显。与瘦子相比，肥胖儿童粪便中的促炎细胞因子和趋化因子（γ干扰素[ifn - γ]、肿瘤坏死因子α [tnf - γ]和单核细胞趋化蛋白1 [MCP-1]）也有平行增加。与非肥胖相关的物种相比，在体外培养的外周血单核细胞中，luti和wexlerae也显示出抗炎作用。我们认为，肠道生态系统中鲁氏杆菌和韦氏杆菌的消耗可能发生在肥胖病例中，并有助于代谢性炎症导致胰岛素抵抗。儿童肥胖是发展胰岛素抵抗的危险因素，如果持续下去，可能导致成年后更严重的疾病，如2型糖尿病（T2D）。我们的研究发现了以前未知的物种，它们的消耗（Blautia luti和Blautia weexlerae）与肥胖个体的胰岛素抵抗有关。我们的研究结果还表明，这些细菌种类可能有助于减少与肥胖相关并发症相关的炎症。童年被认为是解决肥胖问题的机会之窗。因此，这些新发现为未来设计基于微生物群的策略以早期预防肥胖相关并发症提供了有价值的信息。
Cross-sectional studies conducted with obese and control subjects have suggested associations between gut microbiota alterations and obesity, but the links with specific disease phenotypes and proofs of causality are still scarce. The present study aimed to profile the gut microbiota of lean and obese children with and without insulin resistance to characterize associations with specific obesity-related complications and understand the role played in metabolic inflammation. Through massive sequencing of 16S rRNA gene amplicons and data analysis using a novel permutation approach, we have detected decreased incidence of Blautia species, especially Blautia luti and B. wexlerae, in the gut microbiota of obese children, which was even more pronounced in cases with both obesity and insulin resistance. There was also a parallel increase in proinflammatory cytokines and chemokines (gamma interferon [IFN-gamma], tumor necrosis factor alpha [TNF-gamma], and monocyte chemoattractant protein 1 [MCP-1]) in feces of obese children compared to those of lean ones. B. luti and B. wexlerae were also shown to exert an anti-inflammatory effect in peripheral blood mononuclear cell cultures in vitro, compared to non-obesity-associated species. We suggest that the depletion of B. luti and B. wexlerae species in the gut ecosystem may occur in cases of obesity and contribute to metabolic inflammation leading to insulin resistance.IMPORTANCE Child obesity constitutes a risk factor for developing insulin resistance which, if sustained, could lead to more severe conditions like type 2 diabetes (T2D) in adulthood. Our study identified previously unknown species whose depletion (Blautia luti and Blautia wexlerae) is associated with insulin resistance in obese individuals. Our results also indicate that these bacterial species might help to reduce inflammation causally linked to obesity-related complications. Childhood is considered a window of opportunity to tackle obesity. These new findings provide, therefore, valuable information for the future design of microbiota-based strategies for the early prevention of obesity-related complications.