Integrative serum proteomic and metabolomic profiling in ovarian endometrioma: an exploratory multi-omics study

Multi-omics profiling identifies an immunometabolic signature associated with endometriosis

Background Endometriosis (EM) is a chronic inflammatory gynaecological disorder affecting approximately 10% of women of reproductive age. Early diagnosis remains challenging because definitive diagnosis still relies on invasive surgical confirmation. This study aimed to characterize systemic immune-metabolic alterations in EM and identify candidate peripheral blood biomarkers through integrated multi-omics profiling. Methods Peripheral blood samples were collected from 88 participants, including 44 patients with EM T, 22 patients with benign ovarian cysts, and 22 healthy controls. Inflammatory proteomic profiling was performed using the Olink Target 96 Inflammation panel, and untargeted metabolomic analysis was conducted using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). Differential expression, pathway enrichment, integrative network analysis, and receiver operating characteristic (ROC) analyses with bootstrap resampling and false discovery rate (FDR) correction were performed. Results Proteomic analysis revealed significant dysregulation of immune-inflammatory pathways in EM, characterized by enhanced chemokine signaling, cytokine-receptor interactions, and apoptotic activation. Metabolomic profiling identified substantial disturbances in energy metabolism, particularly involving fatty acid β-oxidation, acylcarnitine transport, and amino acid-carbon metabolic reprogramming. Integrated network analysis revealed a candidate immune-metabolic network comprising FGF21, CCL23, CDCP1, and CD8A. Correlation analysis demonstrated that FGF21 was positively associated with lipid oxidation-related metabolites, whereas CCL23 correlated with acylcarnitine species, indicating coordinated immune-metabolic interactions. ROC analyses showed that selected metabolite markers demonstrated moderate discriminatory performance between EM and healthy controls, while combined proteomic-metabolomic models achieved superior diagnostic performance compared with individual markers. Conclusion Multi-omics profiling revealed coordinated immunometabolic alterations associated with EM, characterized by interconnected inflammatory and metabolic alterations in peripheral blood. These findings provide evidence that systemic immune-metabolic dysregulation is associated with EM and support further evaluation of blood-based biomarker strategies for non-invasive detection. However, these findings are based on a single-center cohort and require validation in independent populations and targeted assays.

Metabolic profiling of human follicular fluid to unravel the pathways involved in polycystic ovary syndrome – a systematic review

Polycystic ovary syndrome (PCOS), an endocrine-metabolic disorder, affects women of reproductive age. Follicular fluid (FF) reflects the biochemical microenvironment surrounding the oocyte, providing valuable insight into molecular mechanisms associated with PCOS. Metabolomics enables comprehensive profiling of small-molecule metabolites allowing the identification of disease-specific metabolic signatures, dysregulated pathways, and potential diagnostic/therapeutic targets. This systematic review summarizes available evidence on the FF metabolomic profile of women with PCOS compared to normo-ovulatory controls, aiming to identify PCOS-specific metabolic signatures and dysregulated metabolic pathways. PubMed, Web of Science, and Scopus were searched up to September 2025. Eligible studies were conducted in humans, included at least one group of women with PCOS and a control group with normal ovarian function and normal-weight. Thirty-one studies were included. FF from women with PCOS exhibited consistent metabolomic signatures across analytical platforms and cohorts. The most robust differences involved extensive lipidome alterations, along with amino acid and energy metabolism disturbances. Steroidogenic profiles showed higher testosterone and androsterone sulfate levels, while progesterone, 17-hydroxyprogesterone, and pregnenolone were decreased, suggesting impaired steroidogenesis. Fatty acid alterations included increased saturated, monounsaturated, and polyunsaturated fatty acids. Phosphatidylethanolamine species, triglycerides, and prostaglandin E2 were elevated, whereas phosphatidylcholine and lysophosphatidic acid species were reduced. Among water-soluble metabolites, isoleucine, succinate, malate, glycerol, hypoxanthine, and uracil were increased, while threonine, glutamine, arginine, citrulline, and 4PY were decreased. FF metabolomics reveals a PCOS signature characterized by lipid, amino acid, and energy metabolism dysregulation, potentially contributing to follicular dysfunction. Future studies should consider PCOS phenotypic heterogeneity.

Integrative analysis of transcriptomics and metabolomics reveals mitochondria function genes and associated metabolite pathways in endometritis.

Endometritis is an inflammatory endometrium condition affecting reproductive outcomes. However, the pathology of endometritis is poorly understood. Thus, we attempted to investigate the pathogenic mechanism of endometritis and discover potential biomarkers. Transcriptome sequencing was performed on endometritis patient-derived endometrial tissues (n = 3) and normal controls (n = 5). Differentially expressed genes (DEGs) between disease and control groups were identified. Mitochondrial genes were filtered based on MitoCarta3.0. Small RNA sequencing (9 disease samples vs. 6 controls) was combined with differentially expressed (DE) mitochondrial genes to generate a competing endogenous RNA (ceRNA) network, followed by protein-protein interaction network analysis. Metabolome analysis was conducted to explore differentially expressed metabolites (4 cases vs. 4 controls). Comparative analysis revealed a total of 1,507 DEGs in disease group relative to controls, which were implicated in adaptive immune response, cell chemotaxis, and chemotaxis signaling pathways. In total, 28 mitochondrial genes were differentially expressed and mapped to the ceRNA network. ALDH3A2, ACSS3, CYP24A1, and KMO were identified as hub genes and were closely associated with the infiltration of CD8 T cells. CYP24A1 was found to be the target of four drugs, including calcitriol and deferasirox. Five metabolic pathways were significantly enriched, including the citrate cycle (TCA cycle) and taurine and hypotaurine metabolism. ALDH3A2, ACSS3, and KMO showed interactions with metabolites and significant pathways. Hub genes (ALDH3A2 and ACSS3) play critical roles in the pathogenesis of endometritis by interacting with different metabolites. Our study offers candidate biomarkers for diagnosing and treating endometritis.

Serum metabolic characteristics of interstitial lung disease: a potential link between endocrine aging and gut-derived metabolites.

Objective To analyze differences in serum metabolic profiles between patients with interstitial lung disease (ILD) and healthy controls in northern China using untargeted metabolomics techniques, to identify differentially expressed metabolites and key dysregulated pathways, and to identify potential metabolic biomarkers. Methods Thirty patients with interstitial lung disease (ILD) and 30 healthy controls were enrolled. Untargeted metabolomics analysis was performed using LC-MS/MS in both positive and negative ion modes. Differentially expressed metabolites were identified using the criteria VIP > 1.0, FC > 1.2 or FC < 0.833 and P-value < 0.05. Pathway enrichment analysis was conducted using the KEGG database, and diagnostic performance was evaluated using ROC curves. Results The global metabolic profile showed significant separation between the ILD group and the control group. Pathway enrichment analysis revealed significant dysregulation in lipid metabolism (particularly linoleic acid metabolism), amino acid biosynthesis, and steroid hormone metabolism. GSEA analysis further confirmed the suppression of overall metabolic activity and the specific enrichment of tryptophan metabolism. Among the differentially expressed metabolites, DG(15:0/18:2(9Z,12Z)/0:0) (AUC = 0.914), Medroxalol (AUC = 0.912), estriol 3-sulfate (AUC = 0.890) and DHEA-S (AUC = 0.877) demonstrated high diagnostic value. Conclusion Untargeted metabolomics has revealed significant systemic metabolic dysregulation in ILD. The biomarkers and "metabolic-immune-endocrine" interaction patterns identified offer potential leads for early diagnosis and targeted treatment, which require validation in larger cohorts.

Integrated Multi-Omics Analysis of Gut Microbiota-Associated Metabolites and Related Host Molecular Signatures in Cervical Squamous Cell Carcinoma.

Integrated multi-omics and functional analyses reveal a GDCA-TGR5-mediated immunometabolic signature in anorexia nervosa.