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与心脏代谢疾病管理中药物治疗策略相关的微生物特征

Microbial Features Linked to Medication Strategies in Cardiometabolic Disease Management.

作者信息

Shearer Jane, Shah Shrushti, Shen-Tu Grace, Schlicht Kristina, Laudes Matthias, Mu Chunlong

机构信息

Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada.

Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta T2N 1N4, Canada.

出版信息

ACS Pharmacol Transl Sci. 2024 Feb 5;7(4):991-1001. doi: 10.1021/acsptsci.3c00261. eCollection 2024 Apr 12.

Abstract

Human gut microbiota are recognized as critical players in both metabolic disease and drug metabolism. However, medication-microbiota interactions in cardiometabolic diseases are not well understood. To gain a comprehensive understanding of how medication intake impacts the gut microbiota, we investigated the association of microbial structure with the use of single or multiple medications in a cohort of 134 middle-aged adults diagnosed with cardiometabolic disease, recruited from Alberta's Tomorrow Project. Predominant cardiometabolic prescription medication classes (12 total) were included in our analysis. Multivariate Association with Linear Model () was employed and results were corrected for age, BMI, sex, and diet to evaluate the relationship between microbial features and single- or multimedication use. Highly individualized microbiota profiles were observed across participants, and increasing medication use was negatively correlated with α-diversity. A total of 46 associations were identified between microbial composition and single medications, exemplified by the depletion of by β-blockers and statins, and the enrichment of / and depletion of by metformin. Metagenomics prediction further indicated alterations in microbial functions associated with single medications such as the depletion of enzymes involved in energy metabolism encoded by due to β-blocker use. Specific dual medication combinations also had profound impacts, including the depletion of and by statin plus metformin. Together, these results show reductions in bacterial diversity as well as species and microbial functional potential associated with both single- and multimedication use in cardiometabolic disease.

摘要

人类肠道微生物群被认为是代谢疾病和药物代谢中的关键参与者。然而,心血管代谢疾病中药物与微生物群的相互作用尚未得到充分了解。为了全面了解药物摄入如何影响肠道微生物群,我们在从艾伯塔省明日项目招募的134名被诊断患有心血管代谢疾病的中年成年人队列中,研究了微生物结构与单一或多种药物使用之间的关联。我们的分析纳入了主要的心血管代谢处方药类别(共12种)。采用多元线性模型关联分析,并对年龄、体重指数、性别和饮食进行校正,以评估微生物特征与单一或多种药物使用之间的关系。在参与者中观察到高度个性化的微生物群谱,药物使用增加与α多样性呈负相关。在微生物组成与单一药物之间共鉴定出46种关联,例如β受体阻滞剂和他汀类药物导致的 减少,以及二甲双胍导致的 / 增加和 减少。宏基因组学预测进一步表明,与单一药物相关的微生物功能发生了改变,例如由于使用β受体阻滞剂, 编码的参与能量代谢的酶减少。特定的双联药物组合也有深远影响,包括他汀类药物加二甲双胍导致的 和 减少。总之,这些结果表明,在心血管代谢疾病中,单一和多种药物使用均与细菌多样性、物种及微生物功能潜力的降低有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a93/11040554/cae156665e80/pt3c00261_0001.jpg

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