Jiang Junyi, Zhu Peng, Ding Xiaoying, Zhou Li, Li Xiaoqiang, Lei Yuyan, Wang Hao, Chen LuLu, Li Xiang, Fei Yunzhou, Ouyang Dongsheng, Li Xiaohui, Zhang Wei
Engineering Research Center of Applied Technology of Pharmacogenomics (Ministry of Education, China), Hunan Key Laboratory of Pharmacomicrobiomics, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd, Changsha, 410221, People's Republic of China.
Appl Microbiol Biotechnol. 2025 Apr 22;109(1):97. doi: 10.1007/s00253-025-13481-7.
Previous studies have established a correlation between the microbiome-derived metabolite trimethylamine N-oxide (TMAO) and decreased renal function, but with great heterogeneity. Moreover, population-based evidence remains scarce, particularly in Chinese populations. We designed a meta-analysis and a population-based cross-sectional study in China to examine the associations between TMAO and chronic kidney disease (CKD). In meta-analysis, among 2125 pooled subjects with 1240 controls and 885 CKD patients, a significant association was observed between TMAO and CKD, with a standardized mean difference of - 0.93 (95% confidence interval: - 1.11, - 0.75). Meta-regression analysis identified gender, age, and body mass index (BMI) as significant heterogeneity factors. In our population-based study of 5584 subjects with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m from Sijing community, 100 developed CKD in 2 years. We matched 195 controls by age and gender from the 5484 non-CKD subjects. Male subjects and alcohol consumers exhibited a lower risk of CKD with adjusted odds ratio (OR) of 0.471 (P < 0.05) and 0.320 (P < 0.05), respectively. When comparing subjects in the lowest tertile of TMAO, adjusted OR reached to 1.243 (P > 0.05) for those in the middle and 2.123 (P < 0.05) in the highest tertile (P for trend < 0.05). TMAO demonstrated a moderate capacity to distinguish CKD from non-CKD subjects (AUC = 0.614, P < 0.01). Our findings indicate TMAO is significantly associated with the risk of CKD, and suggest age, gender, and BMI may confound the relationship between TMAO and CKD. KEY POINTS: • Subjects with elevated TMAO levels have an increased risk of CKD. • TMAO demonstrates a moderate capacity to distinguish CKD from non-CKD cases. • Age, gender and BMI may confound the relationship between TMAO and CKD.
以往研究已证实微生物群衍生代谢物氧化三甲胺（TMAO）与肾功能下降之间存在关联，但存在很大异质性。此外，基于人群的证据仍然匮乏，尤其是在中国人群中。我们在中国设计了一项荟萃分析和一项基于人群的横断面研究，以检验TMAO与慢性肾脏病（CKD）之间的关联。在荟萃分析中，在2125名汇总受试者中，有1240名对照者和885名CKD患者，观察到TMAO与CKD之间存在显著关联，标准化平均差为-0.93（95%置信区间：-1.11，-0.75）。元回归分析确定性别、年龄和体重指数（BMI）为显著的异质性因素。在我们对来自泗泾社区的5584名估计肾小球滤过率（eGFR）≥60 mL/min/1.73 m²的受试者进行的基于人群的研究中，有100人在2年内发展为CKD。我们从5484名非CKD受试者中按年龄和性别匹配了195名对照者。男性受试者和饮酒者患CKD的风险较低，调整后的优势比（OR）分别为0.471（P<0.05）和0.320（P<0.05）。当比较TMAO处于最低三分位数的受试者时，处于中间三分位数的受试者调整后的OR为1.243（P>0.05），处于最高三分位数的受试者调整后的OR为2.123（P<0.05）（趋势P<0.05）。TMAO具有中等能力区分CKD受试者和非CKD受试者（曲线下面积=0.614，P<0.01）。我们的研究结果表明TMAO与CKD风险显著相关，并提示年龄、性别和BMI可能混淆TMAO与CKD之间的关系。要点：•TMAO水平升高的受试者患CKD的风险增加。•TMAO具有中等能力区分CKD病例和非CKD病例。•年龄、性别和BMI可能混淆TMAO与CKD之间的关系。
