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胰岛素抵抗与病态肥胖患者阑尾样本中的特定肠道微生物群有关。

Insulin resistance is associated with specific gut microbiota in appendix samples from morbidly obese patients.

作者信息

Moreno-Indias Isabel, Sánchez-Alcoholado Lidia, García-Fuentes Eduardo, Cardona Fernando, Queipo-Ortuño Maria Isabel, Tinahones Francisco J

机构信息

Clinical Management Unit of Endocrinology and Nutrition, Laboratory of The Biomedical Research Institute of Malaga (IBIMA), Virgen de la Victoria University Hospital, Malaga UniversityMalaga, Spain; Biomedical Research Networking Center for Pathophysiology of Obesity and NutritionMadrid, Spain.

Clinical Management Unit of Endocrinology and Nutrition, Laboratory of The Biomedical Research Institute of Malaga (IBIMA), Virgen de la Victoria University Hospital, Malaga University Malaga, Spain.

出版信息

Am J Transl Res. 2016 Dec 15;8(12):5672-5684. eCollection 2016.

Abstract

Alterations in intestinal microbiota composition could promote a proinflammatory state in adipose tissue that is associated with obesity and insulin resistance. Our aim was to identify the gut microbiota associated with insulin resistance in appendix samples from morbidly obese patients classified in 2 groups, high (IR-MO) and low insulin-resistant (NIR-MO), and to determine the possible association between these gut microbiota and variables associated with insulin resistance and the expression of genes related to inflammation and macrophage infiltration in adipose tissue. Appendix samples were obtained during gastric bypass surgery and the microbiome composition was determined by 16S rRNA pyrosequencing and bioinformatics analysis by QIIME. The Chao and Shannon indices for each study group suggested similar bacterial richness and diversity in the appendix samples between both study groups. 16S rRNA pyrosequencing showed that the IR-MO group had a significant increase in the abundance of , , , , , , , , and compared to the NIR-MO group. Moreover, in the IR-MO group we found a significant positive correlation between the abundance of , , and and the visceral adipose tissue expression level of IL6, TNF alpha, ILB1 and CD11b respectively, and significant negative correlations between the abundance of and , and plasma glucose and insulin levels, respectively. In conclusion, an appendix dysbiosis occurs in IR-MO patients, with a loss of butyrate-producing bacteria, essential to maintenance of gut integrity, together with an increase in mucin-degrading bacteria and opportunistic pathogens. The microbiota present in the IR-MO group were related to low grade inflammation in adipose tissue and could be useful for developing strategies to control the development of insulin resistance.

摘要

肠道微生物群组成的改变可促进脂肪组织中的促炎状态,这与肥胖和胰岛素抵抗相关。我们的目的是在分为高胰岛素抵抗(IR-MO)和低胰岛素抵抗(NIR-MO)两组的病态肥胖患者的阑尾样本中,鉴定与胰岛素抵抗相关的肠道微生物群,并确定这些肠道微生物群与胰岛素抵抗相关变量以及脂肪组织中与炎症和巨噬细胞浸润相关基因表达之间的可能关联。在胃旁路手术期间获取阑尾样本,并通过16S rRNA焦磷酸测序和QIIME进行生物信息学分析来确定微生物群组成。每个研究组的Chao和Shannon指数表明,两个研究组的阑尾样本中细菌丰富度和多样性相似。16S rRNA焦磷酸测序显示,与NIR-MO组相比,IR-MO组中 、 、 、 、 、 、 、 和 的丰度显著增加。此外,在IR-MO组中,我们分别发现 、 、 和 的丰度与IL6、TNFα、ILB1和CD11b在内脏脂肪组织中的表达水平之间存在显著正相关,以及 与 、血浆葡萄糖和胰岛素水平之间分别存在显著负相关。总之,IR-MO患者发生阑尾生态失调,产生丁酸盐的细菌减少,而丁酸盐对维持肠道完整性至关重要,同时粘蛋白降解细菌和机会致病菌增加。IR-MO组中存在的微生物群与脂肪组织中的低度炎症有关,可能有助于制定控制胰岛素抵抗发展的策略。

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