Gut microbiota-immune-brain axis: Mechanisms, Implications, and Therapeutic Potential

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About this Research Topic

Submission deadlines

  1. Manuscript Summary Submission Deadline 15 December 2025 | Manuscript Submission Deadline 4 April 2026

  2. This Research Topic is currently accepting articles.

Background

The gut microbiota-immune-brain axis is a bidirectional communication network linking the gut microbiome, immune system, and brain. Over the last decade, research has revealed the profound influence of gut microbes on brain function and behavior through immune signaling, microbial metabolites, and direct neural pathways. Studies have linked gut dysbiosis to various neurological and psychiatric disorders, including anxiety, depression, autism spectrum disorder, and neurodegenerative diseases.



Dominant research approaches involve preclinical animal models (germ-free, antibiotic-treated, or fecal microbiota transplantation) and clinical studies analyzing fecal samples, blood biomarkers, and brain imaging. A key finding is that gut microbes can modulate the immune system, influencing neuroinflammation and neurotransmitter production. Recent advances include identifying microbial strains that impact anxiety-like behavior in animal models and demonstrating the potential of fecal microbiota transplantation to improve symptoms in individuals with autism. Research has evolved beyond simple associations toward mechanistic investigations utilizing multi-omics approaches and advanced analytics.



Several limitations hinder progress in gut-brain axis research. Methodological heterogeneity, due to a lack of standardized microbiome analysis protocols, makes it challenging to compare results across studies. Extrapolating findings from animal models to complex human systems creates translational gaps. Establishing definitive causality between gut microbiome changes and brain outcomes is difficult due to confounding factors and observational study designs. Key questions remain regarding the specific microbial species and metabolites responsible for brain effects, the precise molecular mechanisms involved, and the long-term consequences of microbiome modulation.



These insights are scientifically significant as they offer novel therapeutic targets for neurological and psychiatric disorders. Understanding the gut-immune-brain connection could lead to personalized interventions, including targeted probiotics, prebiotics, and dietary modifications. In the future, this research could revolutionize treatment and prevention of brain disorders. Personalized microbiome-based therapies have the potential to improve mental health, cognitive function, and overall well-being, potentially reducing the societal burden of neurological and psychiatric conditions.



In this Research Topic, we seek to address the following goals:



Standardize microbiome analysis protocols to identify microbes, metabolites, and immune signaling molecules affecting the brain.

Refine animal models to enhance the study of neuro-immune interactions triggered by gut microbes.

Design clinical trials incorporating detailed immunological and neuroimaging endpoints.

Discover biomarkers reflecting gut-brain pathway activity.

Develop personalized therapies targeting specific gut-derived molecules or immune pathways impacting brain circuits.

Elucidate molecular mechanisms of microbial influence on neuronal signaling, neuroinflammation, and glial cell function.

Integrate gut-brain immunology into neurological and psychiatric diagnosis and treatment.

We particularly welcome Original Research, Review, Mini Review, Methods, Perspective, and Clinical Trial articles on:



Microbiota-induced neuroinflammation and behavioral deficits: molecular pathways underlying neuroinflammation and behavior.

Microbiota, autoimmunity, and neurological disease: microbiota’s contribution to autoimmunity and therapeutic modulation.

Diet-microbiota-neurotransmitter-behavior: how diet-induced changes in the microbiome influence neurotransmitter signaling and behavior.

Microbial metabolites and neuronal functions: gut-derived metabolites and their impact on synaptic plasticity and behavior.

Gut-brain immune signaling and behavior: effects of dietary changes on gut-microbe-immune-brain signaling.

Microbiota and neural circuit development: how early-life diet shapes microbial colonization and neural circuit development.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

  • Brief Research Report
  • Data Report
  • Editorial
  • General Commentary
  • Hypothesis and Theory
  • Methods
  • Mini Review
  • Opinion
  • Original Research

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Keywords: Gut microbiota-brain axis, neuroimmune signaling, microbiome metabolites, multi-omics integration, AI-driven biomarker discovery

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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