Bidirectional Association of Gut Microbiota-Derived Trimethylamine N-Oxide and its Precursors with Estimated Glomerular Filtration Rate: A Cross-Lagged Cohort Study

IF 3.7 3区 医学 Q2 NUTRITION & DIETETICS
Ruiheng Peng , Peiying Tian , Ying Lu , He Bai , Yani Wu , Bin Liang , Wenli Ruan , Enmao Cai , Xiaohong Zhang , Mingfeng Ma , Liqiang Zheng
{"title":"Bidirectional Association of Gut Microbiota-Derived Trimethylamine N-Oxide and its Precursors with Estimated Glomerular Filtration Rate: A Cross-Lagged Cohort Study","authors":"Ruiheng Peng ,&nbsp;Peiying Tian ,&nbsp;Ying Lu ,&nbsp;He Bai ,&nbsp;Yani Wu ,&nbsp;Bin Liang ,&nbsp;Wenli Ruan ,&nbsp;Enmao Cai ,&nbsp;Xiaohong Zhang ,&nbsp;Mingfeng Ma ,&nbsp;Liqiang Zheng","doi":"10.1016/j.tjnut.2025.02.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>It is unclear whether trimethylamine N-oxide (TMAO) and its precursors are bidirectionally associated with kidney dysfunction.</div></div><div><h3>Objectives</h3><div>This study aims to investigate whether increased TMAO and its precursors are linked to decreased estimated glomerular filtration rate (eGFR) and whether reduced eGFR is associated with elevated TMAO and its precursors.</div></div><div><h3>Methods</h3><div>Our study consists of participants with creatinine, TMAO, and its precursors (choline, carnitine, and betaine) repeatedly measured from the Fuxin rural cohort. We utilized cross-lagged panel models to assess the potential bidirectional associations of TMAO and its precursors with eGFR. Age (≥60 and &lt;60 y) and sex-specified associations and interaction effects were examined using multi-group cross-lagged panel models. The Bonferroni method was applied for multiple comparisons.</div></div><div><h3>Results</h3><div>Of 1746 participants [mean age 59.4 ± 9.3 y, 584 (33%) male], TMAO was inversely related to eGFR after 2 years [cross-lagged coefficient, 95% confidence interval: –0.030, –0.058, –0.002, <em>P</em> = 0.035], and eGFR was negatively associated with carnitine after 2 years (–0.138, –0.198, –0.078, <em>P</em> &lt; 0.001). Subgroup analysis showed significant associations between baseline TMAO and eGFR after 2 years in individuals aged 60 and older (–0.061, –0.107, –0.014, <em>P</em> = 0.011) and between baseline eGFR and carnitine after 2 years in individuals aged 60 and older (–0.093, –0.164, –0.022, <em>P</em> = 0.010), in those under 60 (–0.153, –0.226, –0.079, <em>P</em> &lt; 0.001), and in females (–0.154, –0.229, –0.079, <em>P</em> &lt; 0.001). Additionally, baseline eGFR is nominally associated with choline after 2 years in those aged under 60 (0.092, 0.017, 0.167, <em>P</em> = 0.017) and in males (0.114, 0.015, 0.213, <em>P</em> = 0.025).</div></div><div><h3>Conclusions</h3><div>Deceased eGFR is related to elevated serum carnitine concentrations and may be linked to choline. Conversely, elevated TMAO may be linked to reduced kidney function. This provides novel evidence that managing healthy kidney function helps keep TMAO and its precursors at optimal levels, whereas maintaining low TMAO concentrations reduces risk of kidney disease.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"155 4","pages":"Pages 1057-1067"},"PeriodicalIF":3.7000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nutrition","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022316625000446","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0

Abstract

Background

It is unclear whether trimethylamine N-oxide (TMAO) and its precursors are bidirectionally associated with kidney dysfunction.

Objectives

This study aims to investigate whether increased TMAO and its precursors are linked to decreased estimated glomerular filtration rate (eGFR) and whether reduced eGFR is associated with elevated TMAO and its precursors.

Methods

Our study consists of participants with creatinine, TMAO, and its precursors (choline, carnitine, and betaine) repeatedly measured from the Fuxin rural cohort. We utilized cross-lagged panel models to assess the potential bidirectional associations of TMAO and its precursors with eGFR. Age (≥60 and <60 y) and sex-specified associations and interaction effects were examined using multi-group cross-lagged panel models. The Bonferroni method was applied for multiple comparisons.

Results

Of 1746 participants [mean age 59.4 ± 9.3 y, 584 (33%) male], TMAO was inversely related to eGFR after 2 years [cross-lagged coefficient, 95% confidence interval: –0.030, –0.058, –0.002, P = 0.035], and eGFR was negatively associated with carnitine after 2 years (–0.138, –0.198, –0.078, P < 0.001). Subgroup analysis showed significant associations between baseline TMAO and eGFR after 2 years in individuals aged 60 and older (–0.061, –0.107, –0.014, P = 0.011) and between baseline eGFR and carnitine after 2 years in individuals aged 60 and older (–0.093, –0.164, –0.022, P = 0.010), in those under 60 (–0.153, –0.226, –0.079, P < 0.001), and in females (–0.154, –0.229, –0.079, P < 0.001). Additionally, baseline eGFR is nominally associated with choline after 2 years in those aged under 60 (0.092, 0.017, 0.167, P = 0.017) and in males (0.114, 0.015, 0.213, P = 0.025).

Conclusions

Deceased eGFR is related to elevated serum carnitine concentrations and may be linked to choline. Conversely, elevated TMAO may be linked to reduced kidney function. This provides novel evidence that managing healthy kidney function helps keep TMAO and its precursors at optimal levels, whereas maintaining low TMAO concentrations reduces risk of kidney disease.
肠道微生物来源的三甲胺n -氧化物及其前体与肾小球滤过率的双向关联:一项交叉滞后队列研究。
背景:目前尚不清楚三甲胺n -氧化物(TMAO)及其前体是否与肾功能障碍双向相关。目的:本研究旨在探讨TMAO及其前体升高是否与eGFR降低相关,以及eGFR降低是否与TMAO及其前体升高相关。方法:我们的研究由阜新农村队列中反复测量肌酐,TMAO及其前体(胆碱,肉碱,甜菜碱)的参与者组成。我们使用交叉滞后面板模型(CLPM)来评估TMAO及其前体与eGFR的潜在双向关联。年龄(≥60岁):在1746名参与者中(平均年龄59.4±9.3岁,男性584名(33%)),TMAO在两年后与eGFR呈负相关(交叉滞后系数,95% CI: -0.030, -0.058至-0.002,P=0.035), eGFR在两年后与肉毒碱呈负相关(-0.138,-0.198至-0.078,P)。结论:死亡的eGFR与血清肉毒碱水平升高有关,可能与胆碱有关。相反,TMAO升高可能与肾功能降低有关。这提供了新的证据,表明管理健康的肾脏功能有助于将TMAO及其前体保持在最佳水平,同时维持低TMAO水平可降低肾脏疾病的风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Journal of Nutrition
Journal of Nutrition 医学-营养学
CiteScore
7.60
自引率
4.80%
发文量
260
审稿时长
39 days
期刊介绍: The Journal of Nutrition (JN/J Nutr) publishes peer-reviewed original research papers covering all aspects of experimental nutrition in humans and other animal species; special articles such as reviews and biographies of prominent nutrition scientists; and issues, opinions, and commentaries on controversial issues in nutrition. Supplements are frequently published to provide extended discussion of topics of special interest.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信