异己酸在抗生素暴露与老年人抑郁症风险的关系中的潜在影响

Metabolic Alterations of Short-Chain Organic Acids in the Elderly Link Antibiotic Exposure with the Risk for Depression

短链有机酸代谢变化在抗生素暴露与老年人抑郁症风险关联中的作用

Authors: Shujing Sun, Li Kong, Fangting Hu, Sheng Wang, Menglong Geng, Hongjuan Cao, Xingyong Tao, Fangbiao Tao, Kaiyong Liu

Source: Metabolites

DOI: 10.3390/metabo14120689

Abstract

Background: Our previous study showed that antibiotic exposure was linked to depressive symptomatology in community-dwelling older adults in China. Our current study aims to explore the underlying mechanisms by assessing the intermediated effects of circulating short-chain organic acids (SCOAs) on this association.

Methods: Depressive symptoms were screened by the 30-item Geriatric Depression Scale (GDS-30). Urinary concentrations of antibiotics and serum SCOAs were measured using a liquid chromatography-mass spectrometry method.

Results: Increased exposure to sulfadiazine, azithromycin, tetracyclines, or veterinary antibiotics (VAs) was positively associated with GDS-30 scores. Tetracycline reduced levels of caproic acid, iso-butyric acid, and iso-caproic acid (iso-CA), with iso-CA concentration inversely correlating with GDS-30 scores, while β-hydroxybutyric acids showed a positive correlation. The mediating effect of serum iso-CA on the association between depression and ofloxacin, with a mediating effect of 25.3%, and the association between depression and tetracycline, with a mediating effect of 46.3%, were both statistically significant, indicating partial mediation.

Conclusions: Antibiotics may affect the levels of SCOAs in older adults and could potentially contribute to depressive symptoms by influencing alterations in serum iso-CA levels.

Keywords: antibiotics; biomonitoring; depressive symptoms; short-chain organic acids; the elderly.

摘要

背景：我们之前的研究表明，抗生素暴露与中国社区老年人的抑郁症状有关。本研究旨在通过评估短链有机酸 (short-chain organic acids，SCOAs) 在该关联关系中的中介作用，以探索这一关联的潜在机制。

方法：抑郁症状通过老年抑郁量表 (the 30-item Geriatric Depression Scale，GDS-30) 进行筛查评估。采用高效液相色谱串联质谱法测量尿液中抗生素以及血清中 SCOAs 的浓度水平。

结果：磺胺嘧啶、阿奇霉素、四环素或兽用抗生素（veterinary antibiotics，VAs）暴露水平的增加与 GDS-30 评分呈正相关关系。四环素水平的增加会降低己酸、异丁酸和异己酸 (iso-caproic aci，iso-CA) 的水平，iso-CA 浓度与 GDS-30 评分之间存在反比关系，而β-羟基丁酸则呈正相关关系。血清 iso-CA 在抑郁症与氧氟沙星之间的关联中存在显著的部分中介效应，占比为 25.3%；iso-CA 在抑郁症与四环素之间的关联中也存在显著的部分中介效应，占比为 46.3%。

结论：抗生素暴露可能会影响老年人体内的 SCOAs 水平，并可能通过影响血清 iso-CA 水平的变化而导致抑郁症状风险的发生。

关键词：抗生素，生物监测，抑郁症状，短链有机酸，老年人