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. 2024 Sep 21;20(5):105.
doi: 10.1007/s11306-024-02166-3.

Stool and blood metabolomics in the metabolic syndrome: a cross-sectional study

Mariana Ponce-de-Leon  1   2 , Rui Wang-Sattler  3   4 , Annette Peters  5   4   6   7 , Wolfgang Rathmann  8   9 , Harald Grallert  4   6   10 , Anna Artati  11 , Cornelia Prehn  11 , Jerzy Adamski  12   13   14 , Christa Meisinger #  15 , Jakob Linseisen #  5   15
Affiliations

Stool and blood metabolomics in the metabolic syndrome: a cross-sectional study

Mariana Ponce-de-Leon et al. Metabolomics. .

Abstract

Introduction/objectives: Changes in the stool metabolome have been poorly studied in the metabolic syndrome (MetS). Moreover, few studies have explored the relationship of stool metabolites with circulating metabolites. Here, we investigated the associations between stool and blood metabolites, the MetS and systemic inflammation.

Methods: We analyzed data from 1,370 participants of the KORA FF4 study (Germany). Metabolites were measured by Metabolon, Inc. (untargeted) in stool, and using the AbsoluteIDQ® p180 kit (targeted) in blood. Multiple linear regression models, adjusted for dietary pattern, age, sex, physical activity, smoking status and alcohol intake, were used to estimate the associations of metabolites with the MetS, its components and high-sensitivity C-reactive protein (hsCRP) levels. Partial correlation and Multi-Omics Factor Analysis (MOFA) were used to investigate the relationship between stool and blood metabolites.

Results: The MetS was significantly associated with 170 stool and 82 blood metabolites. The MetS components with the highest number of associations were triglyceride levels (stool) and HDL levels (blood). Additionally, 107 and 27 MetS-associated metabolites (in stool and blood, respectively) showed significant associations with hsCRP levels. We found low partial correlation coefficients between stool and blood metabolites. MOFA did not detect shared variation across the two datasets.

Conclusions: The MetS, particularly dyslipidemia, is associated with multiple stool and blood metabolites that are also associated with systemic inflammation. Further studies are necessary to validate our findings and to characterize metabolic alterations in the MetS. Although our analyses point to weak correlations between stool and blood metabolites, additional studies using integrative approaches are warranted.

Keywords: Blood metabolomics; Metabolic syndrome; Stool metabolomics; Systemic inflammation.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Stool and blood metabolites and the metabolic syndrome. Volcano plots showing results from multiple linear regression analysis for stool and blood metabolites. Dashed line indicates statistical significance threshold adjusted for false discovery rate (FDR). Metabolites with a significant association are colored based on biochemical class
Fig. 2
Fig. 2
Components of the metabolic syndrome and stool metabolites. Heatmap showing significant associations between individual MetS components and stool metabolites. Associations were considered significant when FDR-adjusted P values < 0.05. Regression coefficients, from multiple regression analyses, are represented by colors ranging from red (positive) to blue (negative). Metabolites are grouped by biochemical classes provided by Metabolon. Glu, fasting glucose; TG, triglycerides
Fig. 3
Fig. 3
Components of the metabolic syndrome and blood metabolites. Heatmap showing significant associations between individual MetS components and blood metabolites. Associations were considered significant when FDR-adjusted P values < 0.05. Regression coefficients, from multiple regression analyses, are represented by colors ranging from red (positive) to blue (negative). Metabolites are grouped by biochemical classes provided by Biocrates. HDL, high-density lipoprotein cholesterol; TG, triglycerides; WC, waist circumference; Glu, fasting glucose; BPs, systolic blood pressure; BPd, diastolic blood pressure
Fig. 4
Fig. 4
MetS-associated metabolites and systemic inflammation. Results of linear regression analyses investigating the association between MetS-associated stool (A) and blood (B) metabolites and systemic inflammation. Only significant linear regression coefficients are shown with 95% FDR-adjusted confidence intervals
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