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Mechanistic Insights into Next-Generation Psychobiotics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 546

Special Issue Editor

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
Interests: gut inflammation; precision nutrition; host-diet-gut microbiome interaction; immune response; pre/probiotics; nutritional epigenomics; intestinal microecology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The gut–brain axis has emerged as a fundamental paradigm in neuroscience and physiology, revealing the profound influence of the gut microbiota on mental health and cognitive function. First-generation psychobiotics, primarily probiotic strains with observed neurological benefits, have shown promise in modulating this axis. However, a paradigm shift is underway toward “next-generation psychobiotics”—defined as precisely engineered microbial therapeutics, their metabolites (postbiotics), and tailored nutritional interventions designed for targeted efficacy. Moving beyond correlation, the field now demands a deeper, mechanistic understanding of how these agents influence neurochemistry, immunology, and neural signaling. This research is critical for translating gut microbiome science into validated, effective interventions for psychiatric, neurodevelopmental, and neurodegenerative disorders, addressing a significant unmet clinical need.

We are pleased to invite you to contribute to a Special Issue dedicated to advancing this frontier. This Special Issue aims to collate high-quality research and reviews that elucidate the specific molecular, cellular, and systemic mechanisms through which next-generation psychobiotic compounds and formulations exert their effects on the brain and behavior. By focusing on mechanistic insights—from genomic and metabolomic pathways to immune modulation and barrier integrity—this collection will strengthen the foundational science required for rational design and clinical application.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

(1) Strain-specific mechanisms of action of novel probiotic candidates on neurotransmitter systems (e.g., GABA, serotonin, dopamine pathways);

(2) Role of bacterial metabolites (postbiotics: SCFAs, neurotransmitters, neuroactive peptides) in modulating neuroinflammation, neurogenesis, or blood–brain barrier function;

(3) Engineered microbes (synbiotics, genetically modified probiotics) for targeted delivery of neurotherapeutics;

(4) Gut microbiome-mediated modulation of the HPA axis and stress resilience;

(5) Interactions between psychobiotics, the host immune system, and central nervous system function;

(6) Preclinical and clinical studies employing omics technologies (metagenomics, metabolomics) to decipher mechanistic pathways.

Novel delivery systems and formulations to enhance the bioavailability and efficacy of psychobiotic agents.

We look forward to receiving your contributions.

Dr. Qi Su
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.

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Keywords

  • gut–brain axis
  • psychobiotics
  • next-generation psychobiotics
  • microbiota
  • probiotics
  • postbiotics
  • microbial metabolites

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Published Papers (1 paper)

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Research

21 pages, 10421 KB  
Article
Butyrate Is Associated with the Antidepressant Effects of Weizmannia coagulans BC99: Functional Similarity of a Microbial Metabolite in the Microbiota–Gut–Brain Axis
by Yiqing Zhou, Yuwan Li, Shanshan Tie, Yao Dong, Shuguang Fang, Ying Wu and Shaobin Gu
Int. J. Mol. Sci. 2026, 27(9), 4082; https://doi.org/10.3390/ijms27094082 - 2 May 2026
Viewed by 328
Abstract
Butyrate, a short-chain fatty acid derived from the gut microbiota, has been linked to depression through correlational studies; however, whether it might act as a sufficient downstream mediator of the antidepressant effects of a probiotic remains poorly understood. To explore this, a chronic [...] Read more.
Butyrate, a short-chain fatty acid derived from the gut microbiota, has been linked to depression through correlational studies; however, whether it might act as a sufficient downstream mediator of the antidepressant effects of a probiotic remains poorly understood. To explore this, a chronic unpredictable mild stress (CUMS) rat model was established to evaluate the potential antidepressant effects of Weizmannia coagulans BC99. Behavioral assessments included the sucrose preference test (SPT), forced swim test (FST), tail suspension test (TST), and open field test (OFT). In addition, 16S rRNA sequencing, serum metabolomics, and short-chain fatty acid (SCFA) profiling were performed. Levels of inflammatory cytokines (IL-1β, IL-6, IL-4, and LPS) and brain-derived neurotrophic factor (BDNF) were measured in serum, hippocampus, and colon by ELISA. An independent sodium butyrate supplementation experiment was conducted to test functional sufficiency, and hippocampal BDNF/TrkB/CREB signaling was assessed by Western blotting. Treatment with BC99 was associated with alleviation of CUMS-induced depressive-like behaviors, increased butyrate levels, reduced neuroinflammation (IL-1β, IL-6, LPS, and IL-4), and restored hippocampal BDNF levels. BC99 also enriched butyrate-producing bacterial taxa (e.g., Lactobacillus, Bifidobacterium, Faecalibaculum) and normalized tryptophan and sphingolipid metabolism. Notably, sodium butyrate alone recapitulated several of the behavioral and anti-inflammatory effects observed with BC99 and, as shown by Western blot, partially restored hippocampal BDNF/TrkB/CREB signaling, which was impaired in CUMS rats. Together, these findings suggest that butyrate may be associated with the antidepressant effects of W. coagulans BC99, potentially acting through suppression of neuroinflammation and activation of the BDNF pathway. Our results support further investigation of butyrate-enhancing strategies as a nutritional approach for depression. Full article
(This article belongs to the Special Issue Mechanistic Insights into Next-Generation Psychobiotics)
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