Ju Jingmeng, He Jialin, Ye Bingqi, Li Siqi, Zhao Jiaqi, Chen Wanlan, Zhang Qi, Zhao Wanying, Yang Jialu, Liu Ludi, Li Yi, Xia Min, Liu Yan
Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
Clin Transl Med. 2025 May;15(5):e70348. doi: 10.1002/ctm2.70348.
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.
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.
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.
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.
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.
久坐时间延长是胰岛素抵抗的一个重要危险因素。最近有证据表明，肠道微生物群可能影响胰岛素敏感性的调节，并且在久坐和身体活跃的个体之间表现出不同的特征。然而，微生物代谢是否以及如何介导久坐时间延长所诱导的胰岛素抵抗进展仍不清楚。
纳入560名未接受降糖治疗的男性参与者，使用胰岛素抵抗稳态模型评估（HOMA-IR）来评估胰岛素抵抗。通过宏基因组学鉴定肠道微生物群，使用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。
一组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HOMA-IR中与久坐时间相关变异的31.68%和21.48%。具体而言，Roseburia sp. CAG:471、巴氏肠杆菌和厚壁菌门细菌CAG:83减少，但与久坐时间延长相关的木聚糖解拟杆菌增加，与胰岛素抵抗的发展存在因果关系。此外，与代谢组学的综合分析确定，由于精氨酸生物合成受到抑制，L-瓜氨酸和L-丝氨酸减少，这是将较长久坐时间与增强的胰岛素抵抗联系起来的关键微生物效应物。
总之，我们的研究结果为肠道微生物群在久坐时间过长所诱导的胰岛素抵抗进展中的介导作用提供了见解，并强调了通过微生物群调节干预措施抵消久坐时间过长对胰岛素抵抗的有害影响的可能性。
久坐时间延长导致Roseburia sp. CAG:471和厚壁菌门细菌CAG:83减少，并抑制精氨酸生物合成。L-瓜氨酸和L-丝氨酸减少作为关键微生物效应物介导久坐时间对胰岛素敏感性的不利影响。针对肠道微生物群有望对抗久坐时间过长所诱导的胰岛素抵抗。
