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不同代谢特征受试者的肠道微生物群与血液及内脏脂肪组织中DNA甲基化模式之间的相互作用。

Interactions between the gut microbiome and DNA methylation patterns in blood and visceral adipose tissue in subjects with different metabolic characteristics.

作者信息

Martínez-Montoro José Ignacio, Martín-Núñez Gracia M, González-Jiménez Andrés, Garrido-Sánchez Lourdes, Moreno-Indias Isabel, Tinahones Francisco J

机构信息

Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010, Málaga, Spain.

Instituto de Investigación Biomédica de Málaga (IBIMA)- Plataforma BIONAND, Málaga, Spain.

出版信息

J Transl Med. 2024 Dec 1;22(1):1089. doi: 10.1186/s12967-024-05746-y.

Abstract

BACKGROUND

The gut microbiome has been reported to induce epigenetic modifications in the host, which may be involved in the pathophysiology of metabolic diseases.

OBJECTIVE

To evaluate the potential interactions between the gut microbiome and DNA methylome in subjects with different metabolic characteristics.

METHODS

Sixty-four participants with different metabolic characteristics (i.e., participants without obesity -healthy controls-, and participants with obesity and normal insulin sensitivity/insulin resistance/ type 2 diabetes-T2DM-) were included in this study. A machine learning approach was performed in order to identify distinctive patterns in three omics (gut microbiome, blood DNA methylome, and visceral adipose tissue-VAT- DNA methylome) according to the different study groups.

RESULTS

Robust distinctive distribution patterns of the three different omics were found between healthy controls and patients with obesity; participants with and without T2DM, and patients with obesity with and without insulin resistance. Importantly, strong correlations between the gut microbiome (including Odoribacteriaceae and Christensenllaceae families) and both blood and VAT DNA methylome were found. Moreover, in the entire study population, three main bacterial genera (Sutterella, Collinsella and Eubacterium) were related to the epigenetic regulation of different genes involved in distinct processes related to cellular metabolism and metabolic diseases, including small ubiquitin-related modifier (SUMO) transferase activity or lipid binding.

CONCLUSION

We show that distinctive interactions between the gut microbiome and DNA methylome may occur in subjects with different metabolic characteristics. Further research is needed to elucidate the potential role of these interactions in the pathophysiology of obesity and related comorbidities.

摘要

背景

据报道,肠道微生物群可诱导宿主发生表观遗传修饰,这可能参与代谢性疾病的病理生理过程。

目的

评估具有不同代谢特征的受试者肠道微生物群与DNA甲基化组之间的潜在相互作用。

方法

本研究纳入了64名具有不同代谢特征的参与者(即无肥胖的参与者——健康对照,以及患有肥胖且胰岛素敏感性正常/胰岛素抵抗/2型糖尿病——T2DM——的参与者)。采用机器学习方法,根据不同研究组,识别三个组学(肠道微生物群、血液DNA甲基化组和内脏脂肪组织——VAT——DNA甲基化组)中的独特模式。

结果

在健康对照与肥胖患者之间;患有和未患有T2DM的参与者之间;以及患有和未患有胰岛素抵抗的肥胖患者之间,发现了三种不同组学的强大独特分布模式。重要的是,发现肠道微生物群(包括气味杆菌科和克里斯滕森菌科)与血液和VAT DNA甲基化组之间存在强相关性。此外,在整个研究人群中,三个主要细菌属(萨特氏菌属、柯林斯菌属和真杆菌属)与参与细胞代谢和代谢疾病不同过程的不同基因的表观遗传调控有关,包括小泛素相关修饰物(SUMO)转移酶活性或脂质结合。

结论

我们表明,肠道微生物群与DNA甲基化组之间的独特相互作用可能发生在具有不同代谢特征的受试者中。需要进一步研究以阐明这些相互作用在肥胖及其相关合并症病理生理中的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5233/11610095/c8bca695524c/12967_2024_5746_Fig1_HTML.jpg

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