Metabolomic Markers of Ultra-Processed Food and Incident CKD

Su, Donghan; Chen, Jingsha; Du, Shutong; Kim, Hyun-Ju; Yu, Bing; Wong, Kari E.; Boerwinkle, Eric; Rebholz, Casey M.

doi:10.2215/cjn.0000000000000062

Cited by 17 publications

(4 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study also identified exogenous metabolite catechol sulfate levels and the amino acid metabolite 3-methylglutaconate levels as risk factors for the onset of psoriasis. Catechol sulfate is recognized as one of the biomarkers for the intake of ultra-processed foods, with its metabolite levels significantly correlating with the consumption of such foods ( 48 ) The increased consumption of ultra-processed foods has been reported to elevate the risk of various diseases, including diabetes, depression, and cancer ( 63 – 65 ). Therefore, individuals with psoriasis should limit their intake of ultra-processed foods to prevent the potential risk increase associated with high levels of catechol sulfate metabolites.…”

Section: Discussionmentioning

confidence: 99%

The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study

Yang,

Zheng,

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

ObjectiveTo explore the influence of serum metabolites on the risk of psoriasis.MethodsIn the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance Weighted method and Wald Ratio’s odds ratios, and 95% confidence intervals. False Discovery Rate was used for multiple comparison corrections. Sensitivity analyses were conducted using Cochran’s Q Test, MR-PRESSO. MR-Steiger Test was employed to check for reverse causality. In the validation stage, we sought other sources of psoriasis GWAS data to verify the initial results and used meta-analysis to combine the effect sizes to obtain robust causal relationships. In addition, we also conducted metabolic pathway enrichment analysis on known metabolites that have a causal relationship with the risk of psoriasis in both stages.ResultsIn the initial stage, we identified 112 metabolites causally associated with psoriasis, including 32 metabolite ratios and 80 metabolites (69 known and 11 unknown). In the validation stage, 24 metabolites (16 known, 1 unknown, and 7 metabolite ratios) were confirmed to have a causal relationship with psoriasis onset. Meta-analysis results showed that the overall effect of combined metabolites was consistent with the main analysis in direction and robust in the causal relationship with psoriasis onset. Of the 16 known metabolites, most were attributed to lipid metabolism, with 5 as risk factors and 8 as protective factors for psoriasis. Peptidic metabolite Gamma-glutamylvaline levels had a negative causal relationship with psoriasis, while exogenous metabolite Catechol sulfate levels and amino acid 3-methylglutaconate levels had a positive causal relationship with the disease onset. The metabolites associated with psoriasis risk in the two stages are mainly enriched in the following metabolic pathways: Glutathione metabolism, Alpha Linolenic Acid and Linoleic Acid Metabolism, Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism, Glycerophospholipid metabolism.ConclusionCirculating metabolites may have a potential causal relationship with psoriasis risk, and targeting specific metabolites may benefit psoriasis diagnosis, disease assessment, and treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study

Yang,

Zheng,

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Previous evidence from prospective cohorts indicates a significant correlation between elevated mannose levels and high risk of kidney failure requiring replacement therapy [ 19 ]. Concurrently, mannose has been employed as a biomarker to elucidate the observed association between the consumption of ultra-processed food and chronic kidney disease (CKD) [ 20 ]. These findings align with our own.…”

Section: Discussionmentioning

confidence: 99%

Mannose and glycine: Metabolites with potentially causal implications in chronic kidney disease pathogenesis

Hu,

Jiang

2024

PLoS ONE

View full text Add to dashboard Cite

Background Chronic Kidney Disease (CKD) represents a global health challenge, with its etiology and underlying mechanisms yet to be fully elucidated. Integrating genomics with metabolomics can offer insights into the putatively causal relationships between serum metabolites and CKD. Methods Utilizing bidirectional Mendelian Randomization (MR), we assessed the putatively causal associations between 486 serum metabolites and CKD. Genetic data for these metabolites were sourced from comprehensive genome-wide association studies, and CKD data were obtained from the CKDGen Consortium. Results Our analysis identified four metabolites with a robust association with CKD risk, of which mannose and glycine showed the most reliable causal relationships. Pathway analysis spotlighted five significant metabolic pathways, notably including "Methionine Metabolism" and "Arginine and Proline Metabolism", as key contributors to CKD pathogenesis. Conclusion This study underscores the potential of certain serum metabolites as biomarkers for CKD and illuminates pivotal metabolic pathways in CKD’s pathogenesis. Our findings lay the groundwork for potential therapeutic interventions and warrant further research for validation.

show abstract

“…The study of 5alpha-androstan-3beta-17betadiol disulfate was limited to the field of Alzheimer's disease (AD) [34]. And elevated serum N2, N2-dimethylguanosine was used for chronic kidney disease (CKD) diagnosis [35]. Urinary excretion of N2,N2dimethylguanosine by adults was used for acute leukemia follow-up [36].…”

Section: Discussionmentioning

confidence: 99%

Causal association between 637 human metabolites and ovarian cancer: a mendelian randomization study

Huang,

Lin,

Zheng

2024

BMC Genomics

View full text Add to dashboard Cite

Background Current evidence suggests a significant association between metabolites and ovarian cancer (OC); however, the causal relationship between the two remains unclear. This study employs Mendelian randomization (MR) to investigate the causal effects between different metabolites and OC. Methods In this study, a total of 637 metabolites were selected as the exposure variables from the Genome-wide Association Study (GWAS) database (http://gwas.mrcieu.ac.uk/datasets/). The OC related GWAS dataset (ieu-b-4963) was chosen as the outcome variable. R software and the TwoSampleMR package were utilized for the analysis in this study. MR analysis employed the inverse variance-weighted method (IVW), MR-Egger and weighted median (WM) for regression fitting, taking into consideration potential biases caused by linkage disequilibrium and weak instrument variables. Metabolites that did not pass the tests for heterogeneity and horizontal pleiotropy were considered to have no significant causal effect on the outcome. Steiger’s upstream test was used to determine the causal direction between the exposure and outcome variables. Results The results from IVW analysis revealed that a total of 31 human metabolites showed a significant causal effect on OC (P < 0.05). Among them, 9 metabolites exhibited consistent and stable causal effects, which were confirmed by Steiger’s upstream test (P < 0.05). Among these 9 metabolites, Androsterone sulfate, Propionylcarnitine, 5alpha-androstan-3beta,17beta-diol disulfate, Total lipids in medium VLDL and Concentration of medium VLDL particles demonstrated a significant positive causal effect on OC, indicating that these metabolites promote the occurrence of OC. On the other hand, X-12,093, Octanoylcarnitine, N2,N2-dimethylguanosine, and Cis-4-decenoyl carnitine showed a significant negative causal association with OC, suggesting that these metabolites can inhibit the occurrence of OC. Conclusions The study revealed the complex effect of metabolites on OC through Mendelian randomization. As promising biomarkers, these metabolites are worthy of further clinical validation.

show abstract

Metabolomic Markers of Ultra-Processed Food and Incident CKD

Abstract: Visual Abstract

Cited by 17 publications

References 40 publications

The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study

The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study

Mannose and glycine: Metabolites with potentially causal implications in chronic kidney disease pathogenesis

Causal association between 637 human metabolites and ovarian cancer: a mendelian randomization study

Contact Info

Product

Resources

About