Untargeted and targeted metabolomics reveal bile acid profile changes in rats with ethylene glycol-induced calcium oxalate nephrolithiasis

Zhou, Zijian; Feng, Dexiang; Shi, Dong; Gao, Peng; Wang, Lujia; Wu, Zhenlong

doi:10.1016/j.cbi.2023.110570

Cited by 5 publications

(4 citation statements)

References 55 publications

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“…Decreased butyrate abundance is connected to heightened susceptibility to infections ( He et al, 2022 ). In addition, Ruminococcaceae are involved in bile acid (BA) metabolism ( Pickard et al, 2017 ), they can decompose cholesterol, generate secondary bile acids, and influence the formation of urinary stones ( Zhou et al, 2023 ). A humanized dyslipidemia mouse model demonstrated that Ruminococcaceae UCG010 reduced BA synthesis ( Xu et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

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Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study

He,

Han,

et al. 2024

Front. Microbiol.

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IntroductionThis study explored the causal connections between gut microbiota (GM), urinary tract infection (UTI), and potential metabolite mediators using Mendelian randomization (MR).MethodsWe utilized summary statistics from the most comprehensive and extensive genome-wide association studies (GWAS) available to date, including 196 bacterial traits for GM, 1,091 blood metabolites, 309 metabolite ratios, alongside UTI data from ukb-b-8814 and ebi-a-GCST90013890. Bidirectional MR analyses were conducted to investigate the causal links between GM and UTI. Subsequently, two MR analyses were performed to identify the potential mediating metabolites, followed by a two-step MR analysis to quantify the mediation proportion.ResultsOur findings revealed that out of the total 15 bacterial traits, significant associations with UTI risk were observed across both datasets. Particularly, taxon g_Ruminococcaceae UCG010 displayed a causal link with a diminished UTI risk in both datasets (ukb-b-8814: odds ratio [OR] = 0.9964, 95% confidence interval [CI] = 0.9930–0.9997, P = 0.036; GCST90013890: OR = 0.8252, 95% CI = 0.7217–0.9436, P = 0.005). However, no substantial changes in g_Ruminococcaceae UCG010 due to UTI were noted (ukb-b-8814: β = 0.51, P = 0.87; ebi-a-GCST90013890: β = −0.02, P = 0.77). Additionally, variations in 56 specific metabolites were induced by g_Ruminococcaceae UCG010, with N-acetylkynurenine (NAK) exhibiting a causal correlation with UTI. A negative association was found between g_Ruminococcaceae UCG010 and NAK (OR: 0.8128, 95% CI: 0.6647–0.9941, P = 0.044), while NAK was positively associated with UTI risk (OR: 1.0009; 95% CI: 1.0002–1.0016; P = 0.0173). Mediation analysis revealed that the association between g_Ruminococcaceae UCG010 and UTI was mediated by NAK with a mediation proportion of 5.07%.DiscussionThis MR study provides compelling evidence supporting the existence of causal relationships between specific GM taxa and UTI, along with potential mediating metabolites.

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Section: Discussionmentioning

confidence: 99%

“…secondary bile acids, and influence the formation of urinary stones (Zhou et al, 2023). A humanized dyslipidemia mouse model demonstrated that Ruminococcaceae UCG010 reduced BA synthesis (Xu et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study

He,

Han,

et al. 2024

Front. Microbiol.

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“…Despite the progress in surgical techniques to improve the efficiency of stone removal, the drugs for nephrolithiasis have been impeded due to the lack of full understanding of the pathogenesis [ 2 ]. It is widely accepted that supersaturation and the build-up of CaOx crystals in renal tissues are the main causes of apoptosis and damage to the kidney tubular cells, a process that can lead to the continual occurrence of kidney stones [ 3 ]. Randall’s plaques (RPs) concept is an accepted theory that is used to explain CaOx stone formation [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of the biomarkers related to ferroptosis in calcium oxalate nephrolithiasis

Hou,

Zhong,

et al. 2024

Aging

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Ferroptosis is a specific type of programmed cell death characterized by iron-dependent lipid peroxidation. Understanding the involvement of ferroptosis in calcium oxalate (CaOx) stone formation may reveal potential targets for this condition. The publicly available dataset GSE73680 was used to identify 61 differentially expressed ferroptosis-related genes (DEFERGs) between normal kidney tissues and Randall's plaques (RPs) from patients with nephrolithiasis through employing weighted gene co-expression network analysis (WGCNA). The findings were validated through in vitro and in vivo experiments using CaOx nephrolithiasis rat models induced by 1% ethylene glycol administration and HK-2 cell models treated with 1 mM oxalate. Through WGCNA and the machine learning algorithm, we identified LAMP2 and MDM4 as the hub DEFERGs. Subsequently, nephrolithiasis samples were classified into cluster 1 and cluster 2 based on the expression of the hub DEFERGs. Validation experiments demonstrated decreased expression of LAMP2 and MDM4 in CaOx nephrolithiasis animal models and cells. Treatment with ferrostatin-1 (Fer-1), a ferroptosis inhibitor, partially reversed oxidative stress and lipid peroxidation in CaOx nephrolithiasis models. Moreover, Fer-1 also reversed the expression changes of LAMP2 and MDM4 in CaOx nephrolithiasis models. Our findings suggest that ferroptosis may be involved in the formation of CaOx kidney stones through the regulation of LAMP2 and MDM4.

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“…Some researchers have already conducted metabolic profiling on the urine of RC patients using 1H NMR [ 8 , 9 ] and targeted amino acid methods [ 10 ]. Reports on untargeted metabolomics [ 11 ], lipid metabolism [ 12 ], and bile acid metabolism [ 13 ] in animal models of RC are also on the rise. However, there is a relative scarcity of serum-targeted metabolomics, with the focus being primarily on pediatric RC patients [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Serum metabolomics study reveals a distinct metabolic diagnostic model for renal calculi

Xiong,

Song,

Zhao

et al. 2024

Heliyon

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Untargeted and targeted metabolomics reveal bile acid profile changes in rats with ethylene glycol-induced calcium oxalate nephrolithiasis

Cited by 5 publications

References 55 publications

Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study

Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study

Identification and validation of the biomarkers related to ferroptosis in calcium oxalate nephrolithiasis

Serum metabolomics study reveals a distinct metabolic diagnostic model for renal calculi

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