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Interplay Between Intestinal Bacteria and Epigenetic Markers in Pathogenesis of...
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Interplay Between Intestinal Bacteria and Epigenetic Markers in Pathogenesis of Metabolic and Neuropsychiatric Disorders

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Neuroscience".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 3363

Special Issue Editor

Dr. Shabnam Nohesara

E-Mail Website
Guest Editor
Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA
Interests: gut microbiome; epigenetic marks; metabolic diseases; neuropsychiatric disorders; inflammatory diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Environmental exposures such as microbes, diet, and pharmaceuticals play a key role in the development and progression of various diseases, particularly metabolic and neuropsychiatric disorders. The complexity of these conditions stems from the interplay between the gut microbiota, their metabolites, host genetics, epigenetics, and the immune system. Recent studies highlight that microbiota-derived metabolites, such as short-chain fatty acids, can modulate epigenetic mechanisms by inhibiting histone deacetylases (HDACs) and altering DNA methylation. These metabolites influence gene expression and impact diverse physiological processes, including immune maturation, immune homeostasis, mucosal barrier integrity, host energy metabolism, and the function of body organs like the brain. This Cells Special Issue will focus on the latest advances in research into the interplay between intestinal bacteria and epigenetic markers in disease pathogenesis. Research papers and reviews examining how diet, bioactive compounds, environmental factors, or how microbiome-based therapies influence health outcomes via epigenetic modulation are welcome. Studies exploring mechanistic links between microbial communities and host gene regulation are also encouraged. By assembling interdisciplinary contributions, this issue aims to advance our understanding of microbiome–epigenome interactions and highlight novel therapeutic opportunities in precision medicine.

Dr. Shabnam Nohesara
Guest Editor

Manuscript Submission Information

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Keywords

  • gut microbiome
  • epigenetic marks
  • metabolic diseases
  • neuropsychiatric disorders
  • probiotics
  • prebiotics
  • postbiotics
  • indole derivatives
  • epigeneic metabolites

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Related Special Issue

Published Papers (3 papers)

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Review

26 pages, 893 KB  
Review
Oxidative Stress–Microbiota–Epigenetics Crosstalk: A Missing Link Between Cognition and Social Behavior in Metabolic and Neuropsychiatric Disorders
by Farzad Ashrafi, Soroor Advani, Adrián A. Pinto-Tomás and Dilip V. Jeste
Cells 2026, 15(1), 3; https://doi.org/10.3390/cells15010003 - 19 Dec 2025
Viewed by 114
Abstract
Oxidative stress (OS) reflects a pathologic imbalance between excessive production of reactive oxygen species (ROS) and insufficient antioxidant defenses. Growing evidence indicates that a healthy gut microbiota (GM) is essential for regulating redox homeostasis, whereas gut dysbiosis contributes to elevated ROS levels and [...] Read more.
Oxidative stress (OS) reflects a pathologic imbalance between excessive production of reactive oxygen species (ROS) and insufficient antioxidant defenses. Growing evidence indicates that a healthy gut microbiota (GM) is essential for regulating redox homeostasis, whereas gut dysbiosis contributes to elevated ROS levels and oxidative damage in DNA, lipids, and proteins. This redox disequilibrium initiates a cascade of cellular disturbances—including synaptic dysfunction, altered receptor activity, excitotoxicity, mitochondrial disruption, and chronic neuroinflammation—that can, in turn, impair cognitive and social functioning in metabolic and neuropsychiatric disorders via epigenetic mechanisms. In this review, we synthesize current knowledge on (1) how OS contributes to cognitive and social deficits through epigenetic dysregulation; (2) the role of disrupted one-carbon metabolism in epigenetically mediated neurological dysfunction; and (3) mechanistic links between leaky gut, OS, altered GM composition, and GM-derived epigenetic metabolites. We also highlight emerging microbiota-based therapeutic strategies capable of mitigating epigenetic abnormalities and improving cognitive and social outcomes. Understanding the OS–microbiota–epigenetic interplay may uncover new targetable pathways for therapies aimed at restoring brain and behavioral health. Full article
(This article belongs to the Special Issue Interplay Between Intestinal Bacteria and Epigenetic Markers in Pathogenesis of Metabolic and Neuropsychiatric Disorders)
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25 pages, 1060 KB  
Review
Psychosomatic Disorders, Epigenome, and Gut Microbiota
by Hamid Mostafavi Abdolmaleky, Ahmad Pirani and Giuseppe Pettinato
Cells 2025, 14(24), 1959; https://doi.org/10.3390/cells14241959 - 10 Dec 2025
Cited by 1 | Viewed by 304
Abstract
Psychosomatic disorders are conditions in which physical (somatic) symptoms are triggered or aggravated by psychological distress. These disorders result from complex interactions among the endocrine, central nervous, and immune systems. Emerging evidence indicates that gut microbiota (GM) dysbiosis, epigenetic alterations, and immune system [...] Read more.
Psychosomatic disorders are conditions in which physical (somatic) symptoms are triggered or aggravated by psychological distress. These disorders result from complex interactions among the endocrine, central nervous, and immune systems. Emerging evidence indicates that gut microbiota (GM) dysbiosis, epigenetic alterations, and immune system dysregulation play pivotal roles in the pathogenesis of psychosomatic disorders and may serve as potential biomarkers for disease states and therapeutic outcomes. This review first outlines how epigenetic dysregulation contributes to psychosomatic disorders through altered expression of genes such as GRM2, TRPA1, SLC6A4, NR3C1, leptin, BDNF, NAT15, HDAC4, PRKCA, RTN1, PRKG1, and HDAC7. We then examine current evidence linking psychosomatic disorders with changes in GM composition and GM-derived epigenetic metabolites, which influence immune function and neurobiological pathways. The core focus of this review is on therapeutic interventions—including probiotics, prebiotics, postbiotics, fecal microbiota transplantation, and targeted dietary approaches—that modulate the gut–brain axis through epigenetic mechanisms for the management of psychosomatic disorders. Finally, we highlight the current challenges and future directions in elucidating the interplay between epigenetics, the GM, and psychosomatic disease mechanisms. In this context, human iPSC-derived multicellular organoids may serve as powerful platforms to unravel mechanistic pathways underlying inter-organ interactions. Full article
(This article belongs to the Special Issue Interplay Between Intestinal Bacteria and Epigenetic Markers in Pathogenesis of Metabolic and Neuropsychiatric Disorders)
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28 pages, 933 KB  
Review
Therapeutic Horizons: Gut Microbiome, Neuroinflammation, and Epigenetics in Neuropsychiatric Disorders
by Shabnam Nohesara, Hamid Mostafavi Abdolmaleky, Ahmad Pirani and Sam Thiagalingam
Cells 2025, 14(13), 1027; https://doi.org/10.3390/cells14131027 - 4 Jul 2025
Cited by 6 | Viewed by 2563
Abstract
Neuroinflammation is a hallmark of many neuropsychiatric disorders (NPD), which are among the leading causes of disability worldwide. Emerging evidence highlights the significant role of the gut microbiota (GM)–immune system–brain axis in neuroinflammation and the pathogenesis of NPD, primarily through epigenetic mechanisms. Gut [...] Read more.
Neuroinflammation is a hallmark of many neuropsychiatric disorders (NPD), which are among the leading causes of disability worldwide. Emerging evidence highlights the significant role of the gut microbiota (GM)–immune system–brain axis in neuroinflammation and the pathogenesis of NPD, primarily through epigenetic mechanisms. Gut microbes and their metabolites influence immune cell activity and brain function, thereby contributing to neuroinflammation and the development and progression of NPD. The enteric nervous system, the autonomic nervous system, neuroendocrine signaling, and the immune system all participate in bidirectional communication between the gut and the brain. Importantly, the interaction of each of these systems with the GM influences epigenetic pathways. Here, we first explore the intricate relationship among intestinal microbes, microbial metabolites, and immune cell activity, with a focus on epigenetic mechanisms involved in NPD pathogenesis. Next, we provide background information on the association between inflammation and epigenetic aberrations in the context of NPD. Additionally, we review emerging therapeutic strategies—such as prebiotics, probiotics, methyl-rich diets, ketogenic diet, and medications—that may modulate the GM–immune system–brain axis via epigenetic regulation for the prevention or treatment of NPD. Finally, we discuss the challenges and future directions in investigating the critical role of this axis in mental health. Full article
(This article belongs to the Special Issue Interplay Between Intestinal Bacteria and Epigenetic Markers in Pathogenesis of Metabolic and Neuropsychiatric Disorders)
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