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Metabolites
Special Issues
Metabolic Disorders and Inflammatory Bowel Diseases
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Metabolic Disorders and Inflammatory Bowel Diseases

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: 25 August 2026 | Viewed by 2925

Special Issue Editor

Dr. Fotios S. Fousekis

E-Mail Website
Guest Editor
Department of Gastroenterology, University Hospital of Ioannina, 45500 Ioannina, Greece
Interests: inflammatory bowel disease; endoscopy; translational immunology in IBD
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The interplay between metabolic disorders and inflammatory bowel diseases (IBD) has emerged as a critical field of investigation in recent years. Both conditions—encompassing obesity, diabetes, dyslipidemia, Crohn’s disease, and ulcerative colitis—share complex pathophysiological mechanisms involving chronic inflammation, immune dysregulation, and alterations in gut microbiota. Understanding these shared pathways offers promising opportunities for novel therapeutic and preventive strategies.

This Special Issue aims to explore the bidirectional relationship between metabolic dysfunction and intestinal inflammation. We welcome the submission of original research articles, reviews, and clinical studies addressing metabolic alterations in IBD, the impact of gut microbiome composition on metabolic homeostasis, and the influence of diet, lifestyle, and pharmacological interventions on disease progression. Mechanistic studies that elucidate molecular signaling networks, cytokine pathways, or genetic predispositions are particularly encouraged.

Dr. Fotios S. Fousekis
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 250 words) can be sent to the Editorial Office for assessment.

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

  • inflammatory bowel disease
  • ulcerative colitis
  • crohn’s disease
  • adipose tissue
  • obesity
  • metabolic disorders

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Published Papers (3 papers)

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Research

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25 pages, 7408 KB  
Article
Integrated Metabolomic and Transcriptomic Analyses Reveal Alterations in the Serotonergic Synapse Pathway and a Robust Diagnostic Model in Ulcerative Colitis
by Haiyan Wang, Hanlin Wu, Yuzhen Fu, Xuhan Lv, Chao Li, Yan Jin, Wei Ge and Zenan Wu
Metabolites 2026, 16(4), 263; https://doi.org/10.3390/metabo16040263 - 14 Apr 2026
Viewed by 611
Abstract
Objectives: To overcome the limitations of invasive diagnostic approaches for ulcerative colitis (UC) diagnosis, this study integrates liquid chromatography–mass spectrometry (LC–MS)-based serum metabolomics with mucosal transcriptomics to elucidate the interplay between systemic metabolic perturbations and neuroendocrine signaling in UC pathogenesis. Methods: Serum metabolites [...] Read more.
Objectives: To overcome the limitations of invasive diagnostic approaches for ulcerative colitis (UC) diagnosis, this study integrates liquid chromatography–mass spectrometry (LC–MS)-based serum metabolomics with mucosal transcriptomics to elucidate the interplay between systemic metabolic perturbations and neuroendocrine signaling in UC pathogenesis. Methods: Serum metabolites and mucosal differentially expressed genes (DEGs) were identified through multi-omics profiling. Key neurotransmitter receptor-related genes (NRRGs) were prioritized using three machine learning algorithms: LASSO, Random Forest, and SVM-RFE. A three-gene diagnostic nomogram was developed and rigorously validated across multiple independent cohorts (GSE48958, GSE73661) using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). Results: The integrated analysis revealed 334 dysregulated metabolites and 3093 DEGs, both converging on the serotonergic synapse pathway. Specific molecular alterations were uncovered, including tryptophan depletion linked to the downregulation of SLC6A4, concomitant with abnormal serotonin accumulation and PTGS2-mediated inflammatory responses. The three-gene signature, HTR3C, RPS6KA6, and NETO2, formed a highly robust diagnostic model, achieving an area under the ROC curve (AUC) exceeding 0.96 in both the training cohort and external validation sets. Conclusions: This multi-omics study delineates a neuroimmune mechanism in UC centered on dysregulation of the serotonergic synapse. The resulting three-gene nomogram identifies a candidate biomarker signature that demonstrates strong discriminative potential; however, given the exceptionally high performance metrics, these findings should be interpreted as a preliminary diagnostic framework rather than a clinically validated tool, and its efficacy relative to standard markers like CRP or fecal calprotectin requires further investigation in prospective real-world cohorts. Nonetheless, this study provides critical mechanistic insights into gut–brain axis dysfunction in UC. Full article
(This article belongs to the Special Issue Metabolic Disorders and Inflammatory Bowel Diseases)
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Review

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14 pages, 303 KB  
Review
Back to the Future: Repurposing Metformin, a Metabolically Active Drug, to Treat Mild-to-Moderate Ulcerative Colitis
by Elisabetta Antonelli, Alessandra Dell’Era, Giovanni Maconi and Gabrio Bassotti
Metabolites 2026, 16(4), 238; https://doi.org/10.3390/metabo16040238 - 31 Mar 2026
Viewed by 816
Abstract
The incidence of ulcerative colitis, an entity belonging to the inflammatory bowel diseases, is rising worldwide. Due to the unpredictable nature of its clinical flares and the need for chronic treatment, ulcerative colitis has a huge burden of psychological impairment and reduced quality [...] Read more.
The incidence of ulcerative colitis, an entity belonging to the inflammatory bowel diseases, is rising worldwide. Due to the unpredictable nature of its clinical flares and the need for chronic treatment, ulcerative colitis has a huge burden of psychological impairment and reduced quality of life. Although several treatments are available to manage patients with ulcerative colitis, their efficacy is unpredictable, and long-term remission is often difficult to achieve. Moreover, the more recent and expensive drugs are not easily available in many countries. These facts have prompted the research in this field to focus on finding additional treatments for such patients. Among the putative repurposing drugs, metformin, an oral antidiabetic agent used for over seventy years, seems to represent a good candidate. While randomized controlled trials suggest that metformin, as an adjunct to conventional treatments, may improve clinical outcomes in mild-to-moderate ulcerative colitis, population-based observational and genetic studies offer mixed signals regarding its role in long-term disease modification or primary prevention. This, together with the wide availability and the low cost of metformin, might represent a good example of repurposing, as detailed in the present review. However, human mechanistic validation remains limited, underscoring the need for further research. Full article
(This article belongs to the Special Issue Metabolic Disorders and Inflammatory Bowel Diseases)
30 pages, 723 KB  
Review
Metabolic Disorders and Inflammatory Bowel Diseases: Unraveling Shared Pathways and Clinical Interactions
by Fotios Fousekis, Afroditi Lamprou, Maria Saridi, Ioanna Nefeli Mastorogianni, Konstantinos Mpakogiannis, Georgios D. Lianos and Konstantinos H. Katsanos
Metabolites 2026, 16(3), 181; https://doi.org/10.3390/metabo16030181 - 9 Mar 2026
Viewed by 1028
Abstract
Inflammatory bowel diseases (IBDs) and metabolic disorders are increasingly recognized as interconnected conditions that frequently coexist and influence each other’s clinical course. Accumulating evidence indicates that patients with IBD face a substantial burden of obesity, metabolic syndrome, metabolic dysfunction-associated steatotic liver disease, osteoporosis, [...] Read more.
Inflammatory bowel diseases (IBDs) and metabolic disorders are increasingly recognized as interconnected conditions that frequently coexist and influence each other’s clinical course. Accumulating evidence indicates that patients with IBD face a substantial burden of obesity, metabolic syndrome, metabolic dysfunction-associated steatotic liver disease, osteoporosis, and type 2 diabetes. These associations appear to be driven by shared and interacting mechanisms, including intestinal barrier disruption, gut microbiota dysbiosis, chronic systemic inflammation, and adipose tissue-mediated immunometabolic pathways. Metabolic comorbidities may worsen IBD activity, reduce response to therapy, increase complications, and contribute to higher health care utilization. Conversely, intestinal inflammation and commonly used treatments, particularly corticosteroids, can adversely affect glucose metabolism, lipid metabolism, body composition and bone homeostasis. Advanced therapies have demonstrated variable metabolic effects, some of which may be beneficial through suppression of systemic inflammation. Recognition of these bidirectional interactions highlights the importance of routine metabolic screening and integrated, multidisciplinary management. Lifestyle interventions, nutritional optimization and individualized therapeutic strategies represent central parts of comprehensive management. Full article
(This article belongs to the Special Issue Metabolic Disorders and Inflammatory Bowel Diseases)
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