Gut Microbiota–Immune–Brain Axis: Mechanisms, Implications, and Therapeutic Potential

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 bidirectional communication within the gut-immune-brain axis, 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 bidirectional gut-immune-brain connection could lead to personalized interventions. 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.

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

1. Standardize microbiome analysis protocols to identify microbes, metabolites, and immune signaling molecules affecting the brain.
2. Refine animal models to enhance the study of neuro-immune interactions triggered by gut microbes.
3. Design clinical trials incorporating detailed immunological and neuroimaging endpoints.
4. Discover biomarkers reflecting gut-brain pathway activity.
5. Develop personalized therapies targeting specific gut-derived molecules or immune pathways impacting brain circuits.
6. Elucidate molecular mechanisms of microbial influence on neuronal signaling, neuroinflammation, and glial cell function.
7. 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:

Gut to Immune-Brain
o Molecular pathways through which gut dysbiosis triggers neuroinflammation and subsequent behavioral impairments.
o Diet-signalling-behavior: bidirectional influence between diet-induced changes in the microbiome and neurotransmitter/immune signalling and behavior.
o Microbiota, immunity, and disease: microbiota’s contribution to autoimmunity and neurological therapeutic modulation.

Brain to Immune-Gut
o Stress on immune and gut: impact of chronic stress/HPA axis dysregulation on gut microbial composition and immune function.

Brain to Gut / Gut to Brain
o Gut-derived metabolites and their impact on synaptic plasticity and behavior.
o 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
• Case Report
• Classification
• Clinical Trial
• Conceptual Analysis
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• ... View all formats

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

Article types

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

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Conceptual Analysis
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Registered Report
• Review
• Study Protocol
• Systematic Review
• Technology and Code

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.