Paired metabolomics identify associations between fecal and serum metabolites in cardiovascular-kidney-metabolic syndrome
4 affiliations
- 1Department of Nephrology, Xuanwu Hospital, Capital Medical University
- 2Department of Nephrology, The First Hospital of Fangshan District
- 3Department of General Practice, Xuanwu Hospital, Capital Medical University
- 4State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases
Abstract
Background: Whether fecal metabolic alterations are associated with circulating metabolic changes in cardiovascular-kidney-metabolic (CKM) syndrome remains unclear. We compared serum and fecal metabolites between different CKM stages and investigated fecal-serum associations.
Methods: Forty-four participants participated in the cross-sectional study, including 19 subjects in CKM stages 1–2 and 25 subjects in CKM stages 3-4. All participants underwent untargeted serum and fecal metabolomics and fecal microbiome profiling. Exploratory serum proteomics was available for 35 participants. Candidate metabolites were selected according to group differences, annotation confidence and redundancy. CKM-adjusted partial Spearman correlations were calculated for paired metabolites. Bootstrap and leave-one-participant-out analyses assessed stability. Serum-fecal KEGG pathway scores and clinical associations were also examined.
Results: Serum analysis identified 470 annotated, non-exogenous features. Different features were involved in lipid-related, organic acid and steroid-related metabolites. Fecal analysis identified six features after Benjamini-Hochberg (BH) correction. Paired analysis of 17 fecal and 48 serum metabolites identified exploratory eight associations. Serum uridine was associated with fecal 1-palmitoyl lysophosphatidic acid, Asp Ala Phe and PE (16:0/0:0). Serum and fecal pyrimidine metabolism scores were positively correlated after adjustment for CKM group (partial rho = 0.429, P = 0.0041, BH-FDR = 0.0246). Selected metabolites were mainly associated with renal function indicators. The fecal microbiome showed greater genus-level dispersion in stages 3-4. Proteomic analysis identified 221 differential proteins enriched in complement and coagulation, inflammatory and lipid-related pathways.
Conclusions: Paired serum and fecal metabolomics identified a positive association between serum and fecal pyrimidine metabolism scores in CKM syndrome, accompanied by the uridine as an exploratory candidate associated with multiple fecal metabolites.
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BibTeX
@article{zhao2026paired,
title = {{Paired metabolomics identify associations between fecal and serum metabolites in cardiovascular-kidney-metabolic syndrome}},
author = {Zihan Zhao and Jinjie Dai and Yuqing Zou and Xueying An and Yunxi Zhang and Congcong Zhu and Lixiao Hao and Linpei Jia},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1982623},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1982623/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Paired metabolomics identify associations between fecal and serum metabolites in cardiovascular-kidney-metabolic syndrome
AU - Zihan Zhao
AU - Jinjie Dai
AU - Yuqing Zou
AU - Xueying An
AU - Yunxi Zhang
AU - Congcong Zhu
AU - Lixiao Hao
AU - Linpei Jia
PY - 2026
DA - 2026/10/27
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1982623
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1982623/full
AB - Background: Whether fecal metabolic alterations are associated with circulating metabolic changes in cardiovascular-kidney-metabolic (CKM) syndrome remains unclear. We compared serum and fecal metabolites between different CKM stages and investigated fecal-serum associations. Methods: Forty-four participants participated in the cross-sectional study, including 19 subjects in CKM stages 1–2 and 25 subjects in CKM stages 3-4. All participants underwent untargeted serum and fecal metabolomics and fecal microbiome profiling. Exploratory serum proteomics was available for 35 participants. Candidate metabolites were selected according to group differences, annotation confidence and redundancy. CKM-adjusted partial Spearman correlations were calculated for paired metabolites. Bootstrap and leave-one-participant-out analyses assessed stability. Serum-fecal KEGG pathway scores and clinical associations were also examined. Results: Serum analysis identified 470 annotated, non-exogenous features. Different features were involved in lipid-related, organic acid and steroid-related metabolites. Fecal analysis identified six features after Benjamini-Hochberg (BH) correction. Paired analysis of 17 fecal and 48 serum metabolites identified exploratory eight associations. Serum uridine was associated with fecal 1-palmitoyl lysophosphatidic acid, Asp Ala Phe and PE (16:0/0:0). Serum and fecal pyrimidine metabolism scores were positively correlated after adjustment for CKM group (partial rho = 0.429, P = 0.0041, BH-FDR = 0.0246). Selected metabolites were mainly associated with renal function indicators. The fecal microbiome showed greater genus-level dispersion in stages 3-4. Proteomic analysis identified 221 differential proteins enriched in complement and coagulation, inflammatory and lipid-related pathways. Conclusions: Paired serum and fecal metabolomics identified a positive association between serum and fecal pyrimidine metabolism scores in CKM syndrome, accompanied by the uridine as an exploratory candidate associated with multiple fecal metabolites.
SN - 1664-2392
ER -