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Unraveling the Role of Epigenetics and Molecular Genetics in Disease Progression via the Gut–Brain Axis

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 3214

Special Issue Editor


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Guest Editor
School of Life Sciences and Biotechnology, Geonguk National University, Andong 36729, Republic of Korea
Interests: prion diseases; Parkinson’s disease; inflammatory bowel diseases; ulcerative colitis; Crohn’s disease; brain-gut axis
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Special Issue Information

Dear Colleagues,

This Special Issue focuses on unraveling the complex roles of epigenetics and molecular genetics in disease progression mediated by the gut–brain axis. Emerging research has shown that epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, along with genetic variants and polymorphisms, critically shape the gut microbiome, intestinal barrier function, and neuroimmune responses. Disruptions in these regulatory mechanisms can lead to increased gut permeability and systemic inflammation. Moreover, they may contribute to the pathogenesis of neurodegenerative and gastrointestinal diseases. By integrating insights from multi-omics technologies, bioinformatics analyses, and experimental studies in cellular and animal models, this Special Issue aims to shed light on how the gut–brain axis serves as a pivotal conduit linking genetic and epigenetic alterations to disease outcomes. We welcome original research articles, reviews, and perspectives that explore molecular pathways, identify novel biomarkers, and propose therapeutic strategies targeting the gut–brain interplay. Ultimately, this collection seeks to advance our understanding of how gut-driven molecular mechanisms influence brain health and systemic diseases, opening avenues for precision medicine approaches in complex disorders involving the gut–brain axis.

Prof. Dr. Yong-Chan Kim
Guest Editor

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Keywords

  • prion diseases
  • Parkinson’s disease
  • Alzheimer’s disease
  • neurodegenerative disease
  • inflammatory bowel diseases
  • ulcerative colitis
  • Crohn’s disease
  • brain–gut axis
  • bioinformatics
  • polymorphism

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Published Papers (2 papers)

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Research

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20 pages, 5446 KB  
Article
TUDCA Ameliorates Cognitive Impairment in APP/PS1 Mice by Modulating the Microbiota–Gut–Brain Axis
by Minxia Zhan, Hui Chen, Xunzhong Fu, Shijin Tang, Xiaoxian Song, Henghua Li, Liancai Zhu and Bochu Wang
Curr. Issues Mol. Biol. 2026, 48(1), 87; https://doi.org/10.3390/cimb48010087 - 15 Jan 2026
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Abstract
Tauroursodeoxycholic acid (TUDCA), a bile acid conjugate, has been suggested to improve cognition in models of Alzheimer’s disease (AD), although its underlying mechanisms remain unclear. This study aimed to evaluate the effects of TUDCA and its potential pathways in APP/PS1 mice. Behavioral tests, [...] Read more.
Tauroursodeoxycholic acid (TUDCA), a bile acid conjugate, has been suggested to improve cognition in models of Alzheimer’s disease (AD), although its underlying mechanisms remain unclear. This study aimed to evaluate the effects of TUDCA and its potential pathways in APP/PS1 mice. Behavioral tests, assessments of amyloid-β (Aβ) deposition, neuroinflammation, peripheral inflammatory responses, intestinal barrier integrity, and gut microbiota composition were performed, along with pseudo-sterile mouse experiments and fecal microbiota transplantation (FMT). The expression of genes related to the TLR4/NF-κB/NLRP3 pathway was also examined. TUDCA significantly ameliorated cognitive impairments, reduced Aβ accumulation, and suppressed inflammatory responses in both the central nervous system and peripheral tissues. It improved intestinal barrier function and reshaped gut microbial composition by reducing pro-inflammatory taxa. FMT demonstrated that TUDCA-modulated microbiota contributed to improved learning and memory in AD mice, whereas antibiotic-induced pseudo-sterility indicated that TUDCA also exerted cognitive benefits independent of gut flora. Moreover, TUDCA inhibited the activation of the TLR4/NF-κB/NLRP3 pathway. In conclusion, TUDCA alleviates AD-related cognitive deficits partly through modulation of the microbiota–gut–brain axis while also acting via microbiota-independent mechanisms, supporting its potential as a promising therapeutic strategy for AD. Full article
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Review

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34 pages, 6958 KB  
Review
A Novel Integrative Framework for Depression: Combining Network Pharmacology, Artificial Intelligence, and Multi-Omics with a Focus on the Microbiota–Gut–Brain Axis
by Lele Zhang, Kai Chen, Shun Li, Shengjie Liu and Zhenjie Wang
Curr. Issues Mol. Biol. 2025, 47(12), 1061; https://doi.org/10.3390/cimb47121061 - 18 Dec 2025
Cited by 1 | Viewed by 2127
Abstract
Major Depressive Disorder (MDD) poses a significant global health burden, characterized by a complex and heterogeneous pathophysiology insufficiently targeted by conventional single-treatment approaches. This review presents an integrative framework incorporating network pharmacology, artificial intelligence (AI), and multi-omics technologies to advance a systems-level understanding [...] Read more.
Major Depressive Disorder (MDD) poses a significant global health burden, characterized by a complex and heterogeneous pathophysiology insufficiently targeted by conventional single-treatment approaches. This review presents an integrative framework incorporating network pharmacology, artificial intelligence (AI), and multi-omics technologies to advance a systems-level understanding and management of MDD. Its central contribution lies in moving beyond reductionist methods by embracing a holistic perspective that accounts for dynamic interactions within biological networks. The primary objective is to demonstrate how AI-powered integration of multi-omics data—spanning genomics, proteomics, and metabolomics—can enable the construction of predictive network models. These models are designed to uncover fundamental disease mechanisms, identify clinically relevant biotypes, and reveal novel therapeutic targets tailored to specific pathological contexts. Methodologically, the review examines the microbiota–gut–brain (MGB) axis as an illustrative case study, detailing its pathogenic roles through neuroimmune alterations, metabolic dysfunction, and disrupted neuro-plasticity. Furthermore, we propose a translational roadmap that includes AI-assisted biomarker discovery, computational drug repurposing, and patient-specific “digital twin” models to advance precision psychiatry. Our analysis confirms that this integrated framework offers a coherent route toward mechanism-based personalized therapies and helps bridge the gap between computational biology and clinical practice. Nevertheless, important challenges remain, particularly pertaining to data heterogeneity, model interpretability, and clinical implementation. In conclusion, we stress that future success will require integrating prospective longitudinal multi-omics cohorts, high-resolution digital phenotyping, and ethically aligned, explainable AI (XAI) systems. These concerted efforts are essential to realize the full potential of precision psychiatry for MDD. Full article
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