State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
Department of Medicine, The University of Hong Kong, Hong Kong, China.
Gut Microbes. 2024 Jan-Dec;16(1):2416928. doi: 10.1080/19490976.2024.2416928. Epub 2024 Oct 29.
The importance of gut microbes in mediating the benefits of lifestyle intervention is increasingly recognized. However, compared to the bacterial microbiome, the role of intestinal fungi in exercise remains elusive. With our established randomized controlled trial of exercise intervention in Chinese males with prediabetes ( = 39, ClinicalTrials.gov:NCT03240978), we investigated the dynamics of human gut mycobiome and further interrogated their associations with exercise-elicited outcomes using multi-omics approaches.
Clinical variations and biological samples were collected before and after training. Fecal fungal composition was analyzed using the internal transcribed spacer 2 (ITS2) sequencing and integrated with paired shotgun metagenomics, untargeted metabolomics, and Olink proteomics.
Twelve weeks of exercise training profoundly promoted fungal ecological diversity and intrakingdom connection. We further identified exercise-responsive genera with potential metabolic benefits, including Verticillium, Sarocladium, and Ceratocystis. Using multi-omics approaches, we elucidated comprehensive associations between changes in gut mycobiome and exercise-shaped metabolic phenotypes, bacterial microbiome, and circulating metabolomics and proteomics profiles. Furthermore, a machine-learning algorithm built using baseline microbial signatures and clinical characteristics predicted exercise responsiveness in improvements of insulin sensitivity, with an area under the receiver operating characteristic (AUROC) of 0.91 (95% CI: 0.85-0.97) in the discovery cohort and of 0.79 (95% CI: 0.74-0.86) in the independent validation cohort ( = 30).
Our findings suggest that intense exercise training significantly remodels the human fungal microbiome composition. Changes in gut fungal composition are associated with the metabolic benefits of exercise, indicating gut mycobiome is a possible molecular transducer of exercise. Moreover, baseline gut fungal signatures predict exercise responsiveness for diabetes prevention, highlighting that targeting the gut mycobiome emerges as a prospective strategy in tailoring personalized training for diabetes prevention.
肠道微生物在介导生活方式干预的益处方面的重要性日益受到重视。然而，与细菌微生物组相比，肠道真菌在运动中的作用仍然难以捉摸。我们通过在中国患有前驱糖尿病的男性中进行的一项已建立的运动干预随机对照试验（ = 39，ClinicalTrials.gov：NCT03240978），研究了人类肠道真菌组的动态，并使用多组学方法进一步探讨了它们与运动引起的结果的关联。
在训练前后收集临床变化和生物样本。使用内部转录间隔区 2（ITS2）测序分析粪便真菌组成，并与配对的 shotgun 宏基因组学、非靶向代谢组学和 Olink 蛋白质组学相结合。
12 周的运动训练极大地促进了真菌生态多样性和种内连接。我们进一步确定了具有潜在代谢益处的运动反应属，包括Verticillium、Sarocladium 和 Ceratocystis。使用多组学方法，我们阐明了肠道真菌组的变化与运动塑造的代谢表型、细菌微生物组和循环代谢组学和蛋白质组学特征之间的综合关联。此外，使用基于基线微生物特征和临床特征的机器学习算法预测了胰岛素敏感性改善的运动反应性，在发现队列中的 AUC 为 0.91（95%CI：0.85-0.97），在独立验证队列中的 AUC 为 0.79（95%CI：0.74-0.86）（ = 30）。
我们的研究结果表明，剧烈的运动训练显著重塑了人类真菌微生物组的组成。肠道真菌组成的变化与运动的代谢益处相关，表明肠道真菌组是运动的一个可能的分子转导器。此外，基线肠道真菌特征可预测运动反应性，用于预防糖尿病，突出了靶向肠道真菌组作为针对糖尿病预防的个性化训练的潜在策略。
