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Cells
Special Issues
Molecular and Cellular Advances in Gut-Brain Axis
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Molecular and Cellular Advances in Gut-Brain Axis

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

Deadline for manuscript submissions: 20 September 2025 | Viewed by 18080

Special Issue Editors

Prof. Dr. Aditi Bhargava

E-Mail Website
Guest Editor
Department of Ob/Gyn and the Center for Reproductive Sciences, University of California San Francisco, 513 Parnassus Ave, HSE1645, Box 0556, San Francisco, CA 94143-0556, USA
Interests: sex differences; stress; CRF; GPCRs; HPA axis; cell signaling and receptor crosstalk; metabolic disease; mental health; systems biology; neuroendocrinology; neurodegenerative diseases; gut–brain axis
Special Issues, Collections and Topics in MDPI journals
Dr. Radhakrishna Rao

E-Mail Website
Guest Editor
Department of Physiology, University of Tennessee, Memphis, TN, USA
Interests: gut barrier; gut-brain axis; molecular study of gastrointestinal diseases; organization of tight junctions; protein phosphorylation-based cell signaling; junction proteins

Special Issue Information

Dear Colleagues,

The gut microbiome is an organ comprising several hundreds to thousands of species of bacteria, viruses, and fungi. The significance of the gut microbiome was recognized by ancient cultures; however, Western medicine and research are beginning to shed light on the various physiological roles of the microbiome and the cellular and molecular mechanisms behind its function. A myriad of physiological functions that range from digestion to mental health are regulated by the various gut flora. The gut–brain axis is bidirectional and influences a plethora of (patho)physiologies including, but not limited to, obesity, inflammatory bowel disease, functional gastrointestinal diseases, mood disorders, neurodegenerative diseases, cardiovascular health, cancers, and reproductive health. Biological sex, diet, and early-life stressors are some of the most important variables that influence normal physiology and disease outcomes but remains vastly understudied. Advances in “omics” have been crucial in elucidating the mechanisms behind the actions of the gut microbiome. This Special Issue seeks original research articles addressing omics, physiological, behavioral, molecular, and cellular aspects of the gut–brain axis in basic and translational research. Review articles will also be considered.

Prof. Dr. Aditi Bhargava
Dr. Radhakrishna Rao
Guest Editors

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. Cells is an international peer-reviewed open access semimonthly 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

  • gut–brain axis
  • microbiome
  • omics
  • diet
  • biological sex
  • gender
  • early-life stress
  • immunity
  • mental health
  • neurodegenerative diseases
  • metabolic health

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Published Papers (2 papers)

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Review

32 pages, 1292 KiB  
Review
Tryptophan and Its Metabolite Serotonin Impact Metabolic and Mental Disorders via the Brain–Gut–Microbiome Axis: A Focus on Sex Differences
by Mengyang Xu, Ethan Y. Zhou and Haifei Shi
Cells 2025, 14(5), 384; https://doi.org/10.3390/cells14050384 - 6 Mar 2025
Viewed by 1349
Abstract
The crisis of metabolic and mental disorders continues to escalate worldwide. A growing body of research highlights the influence of tryptophan and its metabolites, such as serotonin, beyond their traditional roles in neural signaling. Serotonin acts as a key neurotransmitter within the brain–gut–microbiome [...] Read more.
The crisis of metabolic and mental disorders continues to escalate worldwide. A growing body of research highlights the influence of tryptophan and its metabolites, such as serotonin, beyond their traditional roles in neural signaling. Serotonin acts as a key neurotransmitter within the brain–gut–microbiome axis, a critical bidirectional communication network affecting both metabolism and behavior. Emerging evidence suggests that the gut microbiome regulates brain function and behavior, particularly through microbial influences on tryptophan metabolism and the serotonergic system, both of which are essential for normal functioning. Additionally, sex differences exist in multiple aspects of serotonin-mediated modulation within the brain–gut–microbiome axis, affecting feeding and affective behaviors. This review summarizes the current knowledge from human and animal studies on the influence of tryptophan and its metabolite serotonin on metabolic and behavioral regulation involving the brain and gut microbiome, with a focus on sex differences and the role of sex hormones. We speculate that gut-derived tryptophan and serotonin play essential roles in the pathophysiology that modifies neural circuits, potentially contributing to eating and affective disorders. We propose the gut microbiome as an appealing therapeutic target for metabolic and affective disorders, emphasizing the importance of understanding sex differences in metabolic and behavioral regulation influenced by the brain–gut–microbiome axis. The therapeutic targeting of the gut microbiota and its metabolites may offer a viable strategy for treating serotonin-related disorders, such as eating and affective disorders, with potential differences in treatment efficacy between men and women. This review would promote research on sex differences in metabolic and behavioral regulation impacted by the brain–gut–microbiome axis. Full article
(This article belongs to the Special Issue Molecular and Cellular Advances in Gut-Brain Axis)
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28 pages, 772 KiB  
Review
Gut-Brain Axis: Role of Microbiome, Metabolomics, Hormones, and Stress in Mental Health Disorders
by Ankita Verma, Sabra S. Inslicht and Aditi Bhargava
Cells 2024, 13(17), 1436; https://doi.org/10.3390/cells13171436 - 27 Aug 2024
Cited by 13 | Viewed by 16228
Abstract
The influence of gut microbiome, metabolites, omics, hormones, and stress on general and mental health is increasingly being recognized. Ancient cultures recognized the importance of diet and gut health on the overall health of an individual. Western science and modern scientific methods are [...] Read more.
The influence of gut microbiome, metabolites, omics, hormones, and stress on general and mental health is increasingly being recognized. Ancient cultures recognized the importance of diet and gut health on the overall health of an individual. Western science and modern scientific methods are beginning to unravel the foundations and mechanisms behind some of the ancient beliefs and customs. The gut microbiome, an organ itself, is now thought to influence almost all other organs, ranging from the brain to the reproductive systems. Gut microbiome, metabolites, hormones, and biological sex also influence a myriad of health conditions that range from mental health disorders, obesity, gastrointestinal disorders, and cardiovascular diseases to reproductive health. Here, we review the history and current understanding of the gut–brain axis bidirectional talk in various mental health disorders with special emphasis on anxiety and depressive disorders, whose prevalence has increased by over 50% in the past three decades with COVID-19 pandemic being the biggest risk factor in the last few years. The vagal nerve is an important contributor to this bidirectional talk, but other pathways also contribute, and most remain understudied. Probiotics containing Lactobacillus and Bifidobacterium species seem to have the most impact on improvement in mental health symptoms, but the challenge appears to be maintaining sustained levels, especially since neither Lactobacillus nor Bifidobacterium can permanently colonize the gut. Ancient endogenous retroviral DNA in the human genome is also linked to several psychiatric disorders, including depression. These discoveries reveal the complex and intricately intertwined nature of gut health with mental health disorders. Full article
(This article belongs to the Special Issue Molecular and Cellular Advances in Gut-Brain Axis)
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