Attaye Ilias, Beynon-Cobb Beverley, Louca Panayiotis, Nogal Ana, Visconti Alessia, Tettamanzi Francesca, Wong Kari, Michellotti Gregory, Spector Tim D, Falchi Mario, Bell Jordana T, Menni Cristina
Department of Twin Research, King's College London, St Thomas' Hospital Campus, London SE1 7EH, UK.
Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, Amsterdam, the Netherlands.
iScience. 2024 Feb 5;27(3):109132. doi: 10.1016/j.isci.2024.109132. eCollection 2024 Mar 15.
Chronic kidney disease (CKD) is a major public health burden, with dietary acid load (DAL) and gut microbiota playing crucial roles. As DAL can affect the host metabolome, potentially via the gut microbiota, we cross-sectionally investigated the interplay between DAL, host metabolome, gut microbiota, and early-stage CKD (TwinsUK, n = 1,453). DAL was positively associated with CKD stage G1-G2 (Beta (95% confidence interval) = 0.34 (0.007; 0.7), p = 0.046). After adjusting for covariates and multiple testing, we identified 15 serum, 14 urine, 8 stool, and 7 saliva metabolites, primarily lipids and amino acids, associated with both DAL and CKD progression. Of these, 8 serum, 2 urine, and one stool metabolites were found to mediate the DAL-CKD association. Furthermore, the stool metabolite 5-methylhexanoate (i7:0) correlated with 26 gut microbial species. Our findings emphasize the gut microbiota's therapeutic potential in countering DAL's impact on CKD through the host metabolome. Interventional and longitudinal studies are needed to establish causality.
慢性肾脏病（CKD）是一项重大的公共卫生负担，膳食酸负荷（DAL）和肠道微生物群起着关键作用。由于DAL可能通过肠道微生物群影响宿主代谢组，我们进行了横断面研究，以探究DAL、宿主代谢组、肠道微生物群与早期CKD之间的相互作用（英国双胞胎队列，n = 1453）。DAL与CKD G1 - G2期呈正相关（β（95%置信区间）= 0.34（0.007；0.7），p = 0.046）。在对协变量和多重检验进行校正后，我们确定了15种血清、14种尿液、8种粪便和7种唾液代谢物，主要是脂质和氨基酸，它们与DAL和CKD进展均相关。其中，8种血清、2种尿液和1种粪便代谢物被发现介导了DAL与CKD的关联。此外，粪便代谢物5 - 甲基己酸（i7:0）与26种肠道微生物物种相关。我们的研究结果强调了肠道微生物群在对抗DAL通过宿主代谢组对CKD产生影响方面的治疗潜力。需要进行干预性和纵向研究来确定因果关系。
