Journal of neuroimmunologyMar 26, 2026

How gut microbes may influence brain disorders through immune cell activation and inflammation signals

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 27, 2026

Abstract

Neuroinflammation is recognized as a central driver of neurological and neuropsychiatric disorders.

The microbiota-gut-brain axis plays a critical role in modulating neuroimmune signaling.
Microbial-derived metabolites influence central nervous system homeostasis by affecting microglial maturation and activation.
Cytokine signaling networks, including IL-1β, IL-6, and TNF-α, are regulated by these microbial influences.
Dysbiosis-related inflammation may compromise blood-brain barrier integrity and promote immune system infiltration.
Microbial signals can either amplify or reduce neuroinflammatory responses, affecting vulnerability to various disorders.
Current evidence supports the connection between gut microbial changes and central nervous system immune regulation.

Simplified

Neuroinflammation is increasingly recognized as a central driver of diverse neurological and neuropsychiatric disorders. Within this framework, the microbiota-gut-brain axis (MGBA) has emerged as a critical modulator of neuroimmune signaling rather than a broad systemic regulator. Microbial-derived metabolites and immune mediators influence central nervous system (CNS) homeostasis by shaping microglial maturation and activation, regulating cytokine signaling networks, including IL-1β, IL-6, and TNF-α and modulating inflammasome pathways, such as NLRP3. These immune mechanisms intersect with blood-brain barrier (BBB) integrity, where dysbiosis-associated inflammation and altered short-chain fatty acid (SCFA) production may compromise tight junction stability and promote peripheral immune infiltration. Through immune-glial crosstalk, microbial signals can amplify or attenuate neuroinflammatory cascades, thereby influencing vulnerability to autoimmune, neurodegenerative, and neurodevelopmental disorders. This review synthesizes current mechanistic evidence linking gut microbial perturbations to CNS immune regulation, emphasizing microglial activation, cytokine-mediated signaling, and BBB immunomodulation as core pathways. By reframing the MGBA through a neuroimmune lens, we highlight emerging therapeutic strategies targeting microbiota-driven inflammatory circuits to advance precision interventions for inflammatory brain disorders.

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Competing interests

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

How gut microbes may influence brain disorders through immune cell activation and inflammation signals

Abstract

Full Text

Funding

Competing interests

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