微生物代谢介导久坐行为对胰岛素抵抗的恶化作用

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2025-05-24 DOI:10.1002/ctm2.70348

Jingmeng Ju, Jialin He, Bingqi Ye, Siqi Li, Jiaqi Zhao, Wanlan Chen, Qi Zhang, Wanying Zhao, Jialu Yang, Ludi Liu, Yi Li, Min Xia, Yan Liu

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引用次数: 0

摘要

长时间久坐是胰岛素抵抗的重要危险因素。最近的证据表明，肠道微生物群可能影响胰岛素敏感性的调节，并证明了久坐和体力活动个体之间的独特特征。然而，微生物代谢是否以及如何介导长时间久坐引起的胰岛素抵抗的进展尚不清楚。方法采用胰岛素抵抗稳态模型评估（HOMA-IR）对560名未接受降糖治疗的男性受试者进行胰岛素抵抗评估。通过宏基因组学鉴定肠道微生物群，通过基因分型阵列获得宿主遗传数据，并通过液相色谱质谱法定量血浆代谢物。结果15种与久坐相关的物种和38种与久坐相关的代谢能力分别占久坐时间相关的HOMA-IR变异的31.68%和21.48%。具体来说，Roseburia sp. CAG:471、testinibacter bartlettii和厚壁菌门细菌CAG:83的减少，但与久坐时间相关的拟杆菌（Bacteroides xylanisolvens）的增加，与胰岛素抵抗的发展有因果关系。此外，代谢组学的综合分析发现，由于精氨酸生物合成受到抑制，l -瓜氨酸和l -丝氨酸减少，这是与久坐时间延长和胰岛素抵抗增强有关的关键微生物效应物。总之，我们的研究结果揭示了肠道微生物群在久坐引起的胰岛素抵抗进展中的中介作用，并强调了通过微生物群调节干预来抵消长时间久坐对胰岛素抵抗的有害影响的可能性。长时间久坐会导致Roseburia sp. CAG:471和厚壁菌门细菌CAG:83的消耗，并抑制精氨酸的生物合成。l -瓜氨酸和l -丝氨酸功能下降是久坐时间对胰岛素敏感性不利影响的关键微生物效应因子。瞄准肠道微生物群有望对抗由久坐不动引起的胰岛素抵抗。

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Microbial metabolism mediates the deteriorative effects of sedentary behaviour on insulin resistance

Background

Prolonged sedentary time is a strong risk factor for insulin resistance. Recent evidence indicates that gut microbiota may influence the regulation of insulin sensitivity and demonstrates a distinct profile between sedentary and physically active individuals. However, whether and how microbial metabolism mediates the progression of insulin resistance induced by prolonged sedentary time remains unclear.

Methods

560 male participants without hypoglycaemic therapy were included, and insulin resistance was evaluated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). The gut microbiota was identified through metagenomics, host genetic data were obtained using a genotyping array, and plasma metabolites were quantified by liquid chromatography mass spectrometry.

Results

A panel of 15 sedentary-related species and 38 sedentary-associated metabolic capacities accounted for 31.68% and 21.48% of the sedentary time-related variation in HOMA-IR, respectively. Specifically, decreased Roseburia sp. CAG:471, Intestinibacter bartlettii, and Firmicutes bacterium CAG:83, but increased Bacteroides xylanisolvens related to longer sedentary time, were causally linked to the development of insulin resistance. Furthermore, integrative analysis with metabolomics identified reduced L-citrulline and L-serine, resulting from a suppression of arginine biosynthesis as key microbial effectors linking longer sedentary time to enhanced insulin resistance.

Conclusions

In summary, our findings provide insights into the mediating role of gut microbiota on the progression of insulin resistance induced by excessive sedentary time, and highlight the possibility of counteracting the detrimental effect of prolonged sedentary time on insulin resistance by microbiota-modifying interventions.

Key points

Prolonged sedentary time leads to a depletion of Roseburia sp. CAG:471 and Firmicutes bacterium CAG:83, and suppresses arginine biosynthesis.
Decreased L-citrulline and L-serine function as key microbial effectors mediating the adverse effect of sedentary time on insulin sensitivity.
Targeting gut microbiota holds promise to combat insulin resistance induced by excessive sedentary time.

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.