The causal impact of gut microbiota on circulating adipokine concentrations: a two-sample Mendelian randomization study.

IF 2.4 4区医学 Q3 ENDOCRINOLOGY & METABOLISM Hormones-International Journal of Endocrinology and Metabolism Pub Date : 2024-12-01 Epub Date: 2024-04-02 DOI:10.1007/s42000-024-00553-y

Tongxin Zhang, Jingyu Liu, Xiao Liu, Qian Wang, Huawei Zhang

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Abstract

Purpose: Evidence from previous experimental and observational research demonstrates that the gut microbiota is related to circulating adipokine concentrations. Nevertheless, the debate as to whether gut microbiome composition causally influences circulating adipokine concentrations remains unresolved. This study aimed to take an essential step in elucidating this issue.

Methods: We used two-sample Mendelian randomization (MR) to causally analyze genetic variation statistics for gut microbiota and four adipokines (including adiponectin, leptin, soluble leptin receptor [sOB-R], and plasminogen activator inhibitor-1 [PAI-1]) from large-scale genome-wide association studies (GWAS) datasets. A range of sensitivity analyses was also conducted to assess the stability and reliability of the results.

Results: The composite results of the MR and sensitivity analyses revealed 22 significant causal associations. In particular, there is a suggestive causality between the family Clostridiaceae1 (IVW: β = 0.063, P = 0.034), the genus Butyrivibrio (IVW: β = 0.029, P = 0.031), and the family Alcaligenaceae (IVW: β=-0.070, P = 0.014) and adiponectin. Stronger causal effects with leptin were found for the genus Enterorhabdus (IVW: β=-0.073, P = 0.038) and the genus Lachnospiraceae (NK4A136 group) (IVW: β=-0.076, P = 0.01). Eight candidate bacterial groups were found to be associated with sOB-R, with the phylum Firmicutes (IVW: β = 0.235, P = 0.03) and the order Clostridiales (IVW: β = 0.267, P = 0.028) being of more interest. In addition, the genus Roseburia (IVW: β = 0.953, P = 0.022) and the order Lactobacillales (IVW: β=-0.806, P = 0.042) were suggestive of an association with PAI-1.

Conclusion: This study reveals a causal relationship between the gut microbiota and circulating adipokines and may help to offer novel insights into the prevention of abnormal concentrations of circulating adipokines and obesity-related diseases.

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肠道微生物群对循环脂肪因子浓度的因果影响：一项双样本孟德尔随机研究。

目的：以往的实验和观察研究表明，肠道微生物群与循环脂肪因子浓度有关。然而，关于肠道微生物群的组成是否会对循环脂肪因子浓度产生因果影响的争论仍未解决。本研究旨在为阐明这一问题迈出重要的一步：我们使用双样本孟德尔随机化（MR）对大规模全基因组关联研究（GWAS）数据集中的肠道微生物群和四种脂肪因子（包括脂肪连素、瘦素、可溶性瘦素受体[sOB-R]和纤溶酶原激活剂抑制剂-1[PAI-1]）的遗传变异统计进行了因果分析。此外，还进行了一系列敏感性分析，以评估结果的稳定性和可靠性：结果：磁共振分析和敏感性分析的综合结果显示了 22 项显著的因果关联。其中，梭状芽孢杆菌科1（IVW：β=0.063，P=0.034）、布氏梭状芽孢杆菌属（IVW：β=0.029，P=0.031）和钙钛矿科（IVW：β=-0.070，P=0.014）与脂肪连蛋白之间存在提示性因果关系。Enterorhabdus 属（IVW：β=-0.073，P = 0.038）和 Lachnospiraceae 属（NK4A136 组）（IVW：β=-0.076，P = 0.01）与瘦素的因果效应更强。发现有 8 个候选细菌群与 sOB-R 相关，其中以真菌门（IVW：β=0.235，P=0.03）和梭菌目（IVW：β=0.267，P=0.028）更受关注。此外，Roseburia 属（IVW：β=0.953，P=0.022）和 Lactobacillales 目（IVW：β=-0.806，P=0.042）也提示与 PAI-1 有关：这项研究揭示了肠道微生物群与循环脂肪因子之间的因果关系，有助于为预防循环脂肪因子浓度异常和肥胖相关疾病提供新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hormones-International Journal of Endocrinology and Metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Hormones-International Journal of Endocrinology and Metabolism is an international journal published quarterly with an international editorial board aiming at providing a forum covering all fields of endocrinology and metabolic disorders such as disruption of glucose homeostasis (diabetes mellitus), impaired homeostasis of plasma lipids (dyslipidemia), the disorder of bone metabolism (osteoporosis), disturbances of endocrine function and reproductive capacity of women and men. Hormones-International Journal of Endocrinology and Metabolism particularly encourages clinical, translational and basic science submissions in the areas of endocrine cancers, nutrition, obesity and metabolic disorders, quality of life of endocrine diseases, epidemiology of endocrine and metabolic disorders.