The gut–immune–brain axis in neurological disorders: microbial immunology and host–microbe interactions

The human gut harbors a vast and dynamic microbial ecosystem that extends far beyond its traditional role in digestion. Over the past decade, mounting evidence has firmly established that the gut microbiota is a critical regulator of systemic and neuroimmune homeostasis, functioning through a complex network of bidirectional interactions involving the enteric nervous system, the vagus nerve, the hypothalamic–pituitary–adrenal axis, and the immune system. This tripartite communication network, the gut–immune–brain (GIB) axis, is now recognized as a central determinant of neurodevelopment, neuroinflammation, and the progression of a wide spectrum of neurological disorders. Microbial dysbiosis has been linked to altered immune signaling, disruption of the blood–brain barrier (BBB), and dysfunction of CNS-resident immune cells such as microglia and astrocytes. Together, these processes are implicated in the pathogenesis of neurodevelopmental and neurodegenerative conditions including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), epilepsy, Alzheimer’s disease, and Parkinson’s disease.

While general “gut-brain” topics often address broad dietary interventions, clinical associations, or neurobehavioral phenotypes, this Research Topic focuses strictly on the molecular and cellular mechanisms of microbial immunology at the host-microbe interface. Key host–microbe interactions, including the immunomodulatory roles of microbial metabolites such as short-chain fatty acids (SCFAs), the impact of gut dysbiosis on innate and adaptive immune responses, and the downstream consequences for microglial maturation, lymphocyte polarization, and BBB permeability, remain incompletely understood. The Microbial Immunology section of Frontiers in Immunology is ideally positioned to bridge these disciplines by promoting multidisciplinary research that integrates mechanistic immunology, microbiome science, and translational neuroscience. There is a pressing need for studies that move beyond correlative findings to establish causality, integrating preclinical models, multi-omics datasets, and clinical investigations to unravel the immune-mediated mechanisms by which the microbiota shapes brain function, health, and disease susceptibility.

This Research Topic aims to consolidate and accelerate our understanding of the GIB axis in neurological diseases, emphasizing microbiota-driven immune mechanisms and host–microbe interactions. We welcome Original Research, Reviews, and Translational Perspectives exploring molecular, cellular, and systemic aspects of gut–immune–brain crosstalk. To gather further insights within this interdisciplinary field, we invite submissions addressing — but not limited to — the following themes:

-Microbial dysbiosis and neuroimmunity: immune responses to gut microbial alterations in neurodevelopmental and neurodegenerative disorders.
-Gut-derived metabolites and immune modulation: roles of SCFAs, bile acids, tryptophan derivatives, and neuroactive molecules in regulating neuroinflammation and BBB integrity.
-Microglial and astrocytic regulation: microbiota-driven modulation of CNS-resident immune cells and implications for neuronal plasticity, neurogenesis, and neurodegeneration.
-Innate and adaptive immune signaling: T cell and B cell responses, cytokine networks, and mucosal immunity influencing CNS immune tone.
-Immunometabolism and host–microbe communication: metabolic pathways at the interface of gut microbial activity and neuroimmune regulation.
-Maternal microbiota, neurodevelopment, and immune priming: perinatal programming of neuroimmune outcomes and vulnerability to neurological disorders.
-Therapeutic approaches to the GIB axis: advances in probiotics, prebiotics, postbiotics, dietary strategies, immunotherapies, and fecal microbiota transplantation.
-Systems-level and translational studies: applications of multi-omics, systems biology, and organ-on-a-chip technologies to model GIB axis function and identify biomarkers for clinical translation.

By fostering this integrative perspective, the Topic seeks to promote mechanistic and translational insight into how gut microbiota-driven immune signals shape brain function and disease progression, ultimately driving the development of microbiota- and immune-targeted strategies for improved neurological health.

We welcome Original Research, Reviews, and Translational Perspectives, with a strong focus on mechanistic studies that establish causality rather than mere correlation. Submissions should specifically explore how gut microbiota-driven immune signals, microbial metabolites, and maternal immune priming shape microglial activity, blood–brain barrier integrity, and the progression of neurodevelopmental or neurodegenerative disorders.

The topic editors declare no conflict of interest