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Emerging Roles of the Gut-Brain Axis (GBA) in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 May 2026 | Viewed by 2285

Special Issue Editor


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Guest Editor
Department of Neurology, University of Florida, Gainesville, FL, USA
Interests: electrical stimulation; surgical procedure at the cellular level; gut-brain axis

Special Issue Information

Dear Colleagues,

We invite researchers, clinicians, and scientists to contribute original articles, reviews, and perspectives to our upcoming Special Issue focused on the gut–brain axis (GBA) and its role in health and disease. The GBA is an intricate, bidirectional communication network between the gastrointestinal tract and the central nervous system, involving neural, hormonal, immune, and microbial pathways. Emerging evidence highlights the GBA's pivotal role in regulating mood, cognition, immune responses, and metabolic processes, while its dysregulation has been implicated in a broad spectrum of conditions—from depression, anxiety, and neurodegenerative disorders to irritable bowel syndrome and inflammatory bowel disease.

This issue seeks to explore the latest advances in understanding how the gut microbiota influences brain function and vice versa, and how this knowledge can be harnessed for novel diagnostic tools and therapeutic strategies. We particularly welcome submissions on microbiome research, psychobiotics, nutritional neuroscience, immune signaling, and gut-targeted interventions in neurological and psychiatric disorders.

Join us in advancing this exciting interdisciplinary field by sharing your work. Submissions will undergo rigorous peer review, and selected papers will be featured in a high-impact issue aimed at driving innovation in clinical and translational medicine.

Dr. Vinata Vedam-Mai
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • gut–brain axis
  • gut microbiota
  • brain function
  • diagnostic tools

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Published Papers (2 papers)

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Research

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19 pages, 1877 KB  
Article
Abscopal Brain Proteomic Changes Associated with Microbiome Alterations Induced by Gastrointestinal Acute Radiation Syndrome in Swine
by Kathleen Hatch, Timothy S. Horseman, Babita Parajuli, Erin K. Murphy, Robert N. Cole, Robert N. O’Meally, Daniel P. Perl, David M. Burmeister and Diego Iacono
Int. J. Mol. Sci. 2025, 26(17), 8121; https://doi.org/10.3390/ijms26178121 - 22 Aug 2025
Cited by 1 | Viewed by 1042
Abstract
Emerging research highlights the gut microbiota’s critical role in modulating brain activity via the gut–brain axis. This study explores whether targeted gastrointestinal irradiation induces abscopal effects on the brain proteome, revealing microbiota-mediated neurobiological changes. Male Sinclair minipigs were randomized to receive either sham [...] Read more.
Emerging research highlights the gut microbiota’s critical role in modulating brain activity via the gut–brain axis. This study explores whether targeted gastrointestinal irradiation induces abscopal effects on the brain proteome, revealing microbiota-mediated neurobiological changes. Male Sinclair minipigs were randomized to receive either sham treatment (n = 6) or 8 Gy lower hemibody (gut-targeted) irradiation (n = 5). Over 14 days, rectal swabs were collected to monitor microbiota dynamics, followed by frontal cortex proteomic analysis. Irradiation altered gut microbiota composition, notably reducing Chlamydiae and Firmicutes phyla, while increasing Coriobacteriaceae and Acinetobacter. Proteomic analysis identified 75 differentially abundant proteins in the frontal cortex, including a significant decrease in pannexin-1 (PANX1), suggesting modulation of the NLRP3 inflammasome pathway. Functional enrichment analysis revealed immune and neurotransmission-related changes linked to microbial shifts. These results demonstrate that gut-targeted radiation can remotely affect brain protein expression, emphasizing the microbiota’s role in neuroimmune regulation and pointing to novel therapeutic opportunities in gut–brain axis disorders. Full article
(This article belongs to the Special Issue Emerging Roles of the Gut-Brain Axis (GBA) in Health and Disease)
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Review

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13 pages, 733 KB  
Review
G Protein-Coupled Receptors in Irritable Bowel Syndrome: Mechanisms and Therapeutic Opportunities
by Zhenya Zhu, Ziyu Liu, Yate He, Xiaorui He, Wei Zheng and Mizu Jiang
Int. J. Mol. Sci. 2026, 27(2), 752; https://doi.org/10.3390/ijms27020752 - 12 Jan 2026
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Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain, altered motility, and visceral hypersensitivity. Emerging evidence implicates G protein-coupled receptors (GPCRs) as key integrators of microbial, immune, endocrine, and neural signals in IBS pathophysiology. This review summarizes recent advances [...] Read more.
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain, altered motility, and visceral hypersensitivity. Emerging evidence implicates G protein-coupled receptors (GPCRs) as key integrators of microbial, immune, endocrine, and neural signals in IBS pathophysiology. This review summarizes recent advances in understanding how GPCRs mediate gut immune regulation, microbiota–host crosstalk, metabolic signaling, and pain processing in IBS. Recent studies show that microbial metabolites (e.g., short-chain fatty acids, biogenic amines, and lipid mediators) signal through GPCRs on immune cells, epithelia, and neurons to influence intestinal homeostasis. On immune cells and neurons, GPCRs also mediate signals from external substances (such as fats, sugars, histamine, etc.) to regulate immune and neural functions. And there are challenges and future directions in targeting GPCRs for IBS, including patient heterogeneity and the complexity of host–microbiome interactions. This review provides a mechanistic framework for GPCR-based therapies in IBS. Full article
(This article belongs to the Special Issue Emerging Roles of the Gut-Brain Axis (GBA) in Health and Disease)
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