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Metabolites
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Advances in Metabolomics and Multi-Omics Integration
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Advances in Metabolomics and Multi-Omics Integration

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Integrative Metabolomics".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 5651

Special Issue Editor

Dr. Kurt K. Zhang

E-Mail Website
Guest Editor
Institute of Bioscience and Technology, Texas A&M University, Houston, TX 77030, USA
Interests: multi-omics; cell metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to announce the launch of this Special Issue of Metabolites. This Special Issue aims to report the cutting-edge advancements and methodologies in metabolomics, and its integration with various omics data, including the genome, transcriptome, proteome, epigenome and microbiome.

In this Special Issue, we seek to highlight research that not only advances the science of metabolomics, but also demonstrates innovative strategies for the integration of multiple omics datasets. We invite submissions that cover a range of topics, including, but not limited to, the following:

  • Novel methodologies for metabolomic data acquisition and analysis;
  • Integration techniques for multi-omics data to uncover new insights into cellular and systemic metabolism;
  • Applications of metabolomics and multi-omics in disease diagnosis, prognosis and therapeutics;
  • Case studies demonstrating the utility of metabolomics in conjunction with other omics technologies.

We look forward to your submissions that contribute to this cutting-edge forum on metabolomics and multi-omics research.

Dr. Kurt K. Zhang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolomics
  • cellular metabolism
  • multi-omics
  • metabolites
  • molecular interaction
  • cell–cell cross-talk

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (4 papers)

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Research

17 pages, 7353 KiB  
Article
Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome
by Daniel Kirk, Panayiotis Louca, Ilias Attaye, Xinyuan Zhang, Kari E. Wong, Gregory A. Michelotti, Mario Falchi, Ana M. Valdes, Frances M. K. Williams and Cristina Menni
Metabolites 2025, 15(2), 121; https://doi.org/10.3390/metabo15020121 - 12 Feb 2025
Cited by 1 | Viewed by 1215
Abstract
Background/Objectives: Irritable bowel syndrome (IBS) is a complex disorder affecting 10% of the global population, but the underlying mechanisms remain poorly understood. By integrating multifluid metabolomics, we aimed to identify metabolite markers of IBS in a large population-based cohort. Methods: We [...] Read more.
Background/Objectives: Irritable bowel syndrome (IBS) is a complex disorder affecting 10% of the global population, but the underlying mechanisms remain poorly understood. By integrating multifluid metabolomics, we aimed to identify metabolite markers of IBS in a large population-based cohort. Methods: We included individuals from TwinsUK with and without IBS, ascertained using the Rome III criteria, and analysed serum (232 cases, 1707 controls), urine (185 cases, 1341 controls), and stool (186 cases, 1284 controls) metabolites (Metabolon Inc.). Results: After adjusting for covariates, and multiple testing, 44 unique metabolites (25 novel) were associated with IBS, including lipids, amino acids, and xenobiotics. Androsterone sulphate, a sulfated steroid hormone precursor, was associated with lower odds of IBS in both urine (0.69 [95% confidence interval = 0.56–0.85], p = 2.34 × 10−4) and serum (0.75 [0.63–0.90], p = 1.54 × 10−3. Moreover, suberate (C8-DC) was associated with higher odds of IBS in serum (1.36 [1.15–1.61]; p = 1.84 × 10−4) and lower odds of IBS in stool (0.76 [0.63–0.91]; p = 2.30 × 10−3). On the contrary, 32 metabolites appeared to be fluid-specific, including indole, 13-HODE + 9-HODE, pterin, bilirubin (E,Z or Z,Z), and urolithin. The remaining 10 metabolites were associated with IBS in one fluid with suggestive evidence (p < 0.05) in another fluid. Finally, we identified androgenic signalling, dicarboxylates, haemoglobin, and porphyrin metabolism to be significantly over-represented in individuals with IBS compared to controls. Conclusions: Our results highlight the utility of a multi-fluid approach in IBS research, revealing distinct metabolic signatures across biofluids. Full article
(This article belongs to the Special Issue Advances in Metabolomics and Multi-Omics Integration)
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15 pages, 3128 KiB  
Article
The Comorbidity of Depression and Diabetes Is Involved in the Decidual Protein Induced by Progesterone 1 (Depp1) Dysfunction in the Medial Prefrontal Cortex
by Chen Xu, Mengxing Liao, Shize Zhang, Yuang Chen, Xinyue Shulai, Guangji Wang and Jiye Aa
Metabolites 2025, 15(1), 34; https://doi.org/10.3390/metabo15010034 - 9 Jan 2025
Viewed by 849
Abstract
Background: There is a high rate of depressive symptoms such as irritability, anhedonia, fatigue, and hypersomnia in patients with type 2 diabetes mellitus (T2DM). However, the causes and underlying mechanisms of the comorbidity of depression and diabetes remain unknown. Methods: For the first [...] Read more.
Background: There is a high rate of depressive symptoms such as irritability, anhedonia, fatigue, and hypersomnia in patients with type 2 diabetes mellitus (T2DM). However, the causes and underlying mechanisms of the comorbidity of depression and diabetes remain unknown. Methods: For the first time, we identified Decidual protein induced by progesterone 1 (Depp1), also known as DEPP autophagy regulator 1, as a hub gene in both depression and T2DM models. Depp1 levels were increased in the mPFC but not in other brain regions, such as the hippocampus or nucleus accumbens, according to Western blot and PCR assays. Results: Glucose dysregulation and synaptic loss occur in both depression and T2DM. The typical hyperglycemia in T2DM was observed in two models of depression, namely, chronic social defeat stress (CSDS) and chronic restraint stress (CRS). Hyperglycemia, which occurred in T2DM, was observed, and metabolomics data clearly showed the perturbation of glucose levels and glucose metabolism in the medial prefrontal cortex (mPFC). Decreased protein levels of BDNF and PSD95 suggested significant synaptic loss in depressed and diabetic mice. Conclusion: These findings suggest that the comorbidity of depression and diabetes is involved in the dysfunction of Depp1 in the mPFC. Full article
(This article belongs to the Special Issue Advances in Metabolomics and Multi-Omics Integration)
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28 pages, 7934 KiB  
Article
Transcriptomic Profiling Reveals Altered Expression of Genes Involved in Metabolic and Immune Processes in NDV-Infected Chicken Embryos
by Malarmathi Muthusamy, Kannaki T. Ramasamy, Sunday Olusola Peters, Srinivasan Palani, Vasudevan Gowthaman, Murali Nagarajan, Sivakumar Karuppusamy, Vasanthakumar Thangavelu and Thiruvenkadan Aranganoor Kannan
Metabolites 2024, 14(12), 669; https://doi.org/10.3390/metabo14120669 - 2 Dec 2024
Viewed by 1385
Abstract
Objective: The poultry industry is significantly impacted by viral infections, particularly Newcastle Disease Virus (NDV), which leads to substantial economic losses. It is essential to comprehend how the sequence of development affects biological pathways and how early exposure to infections might affect immune [...] Read more.
Objective: The poultry industry is significantly impacted by viral infections, particularly Newcastle Disease Virus (NDV), which leads to substantial economic losses. It is essential to comprehend how the sequence of development affects biological pathways and how early exposure to infections might affect immune responses. Methods: This study employed transcriptome analysis to investigate host–pathogen interactions by analyzing gene expression changes in NDV-infected chicken embryos’ lungs. Result: RNA-Seq reads were aligned with the chicken reference genome (Galgal7), revealing 594 differentially expressed genes: 264 upregulated and 330 downregulated. The most overexpressed genes, with logFC between 8.15 and 8.75, included C8A, FGG, PIT54, FETUB, APOC3, and FGA. Notably, downregulated genes included BPIFB3 (−4.46 logFC) and TRIM39.1 (−4.26 logFC). The analysis also identified 29 novel transcripts and 20 lncRNAs that were upregulated. Gene Ontology and KEGG pathways’ analyses revealed significant alterations in gene expression related to immune function, metabolism, cell cycle, nucleic acid processes, and mitochondrial activity due to NDV infection. Key metabolic genes, such as ALDOB (3.27 logFC), PRPS2 (2.66 logFC), and XDH (2.15 logFC), exhibited altered expression patterns, while DCK2 (−1.99 logFC) and TK1 (−2.11 logFC) were also affected. Several immune-related genes showed significant upregulation in infected lung samples, including ALB (6.15 logFC), TLR4 (1.86 logFC), TLR2 (2.79 logFC), and interleukin receptors, such as IL1R2 (3.15 logFC) and IL22RA2 (1.37 logFC). Conversely, genes such as CXCR4 (−1.49 logFC), CXCL14 (−2.57 logFC), GATA3 (−1.51 logFC), and IL17REL (−2.93 logFC) were downregulated. The higher expression of HSP genes underscores their vital role in immune responses. Conclusion: Comprehension of these genes’ interactions is essential for regulating viral replication and immune responses during infections, potentially aiding in the identification of candidate genes for poultry breed improvement amidst NDV challenges. Full article
(This article belongs to the Special Issue Advances in Metabolomics and Multi-Omics Integration)
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13 pages, 532 KiB  
Article
Investigating the Link between Intermediate Metabolism, Sexual Dimorphism, and Cardiac Autonomic Dysfunction in Patients with Type 1 Diabetes
by María Rosa Insenser, Lía Nattero-Chávez, Manuel Luque-Ramírez, Sara de Lope Quiñones, Alejandra Quintero-Tobar, Sara Samino, Núria Amigó, Beatriz Dorado Avendaño, Tom Fiers and Héctor F. Escobar-Morreale
Metabolites 2024, 14(8), 436; https://doi.org/10.3390/metabo14080436 - 6 Aug 2024
Cited by 1 | Viewed by 1572
Abstract
Sexual dimorphism influences cardiovascular outcomes in type 1 diabetes (T1D), with women facing a higher relative risk of macrovascular events compared to men, especially after menopause. This study hypothesizes that abnormalities in intermediate metabolism may be associated with cardiac autonomic neuropathy (CAN) in [...] Read more.
Sexual dimorphism influences cardiovascular outcomes in type 1 diabetes (T1D), with women facing a higher relative risk of macrovascular events compared to men, especially after menopause. This study hypothesizes that abnormalities in intermediate metabolism may be associated with cardiac autonomic neuropathy (CAN) in T1D. We aim to assess low molecular weight metabolites (LMWM) as markers of CAN in T1D, considering the effects of sexual dimorphism and age. In this cross-sectional study, we included 323 subjects with T1D (147 women and 176 men), with a mean age of 41 ± 13 years. A total of 44 women and 41 men were over 50 years old. CAN was assessed using Ewing’s tests, and serum metabolites were analyzed by proton nuclear magnetic resonance spectroscopy (1H-NMR). Patients with CAN had lower levels of valine, isoleucine, and threonine, and higher levels of lactate, compared to those without CAN. These differences persisted after adjusting for BMI and estimated glucose disposal rate (eGDR). In a logistic regression model (R² = 0.178, p < 0.001), the main determinants of CAN included isoleucine [Exp(β) = 0.972 (95% CI 0.952; 0.003)], age [Exp(β) = 1.031 (95% CI 1.010; 1.053)], A1c [Exp(β) = 1.361 (95% CI 1.058; 1.752)], and microangiopathy [Exp(β) = 2.560 (95% CI 1.372; 4.778)]. Sex influenced LMWM profiles, with over half of the metabolites differing between men and women. However, no interactions were found between CAN and sex, or between sex, age, and CAN, on metabolomics profiles. Our findings suggest an association between CAN and LMWM levels in T1D. The sexual dimorphism observed in amino acid metabolites was unaffected by the presence of CAN. Full article
(This article belongs to the Special Issue Advances in Metabolomics and Multi-Omics Integration)
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