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Durairaj Ragu Varman
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REVIEW ARTICLE

NOD-like receptor pyrin domain-containing protein 3 inflammasome activation in microbiota-induced neuroinflammation: Relevance to autism and stress disorders

Durairaj Ragu Varman1* ,  Jayakumar Fairen Angelin1
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1 School of Biomedical Sciences, Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, India
MI, 026100024 https://doi.org/10.36922/MI026100024
Received: 5 March 2026 | Revised: 12 June 2026 | Accepted: 8 July 2026 | Published online: 27 July 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The gut–brain axis has evolved into a bidirectional neuroimmune communication network linking microbial ecology, innate immunity, endocrine signaling, and central nervous system function. The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a key cytosolic sensor that converts signals from microbes into pro-inflammatory pathways. Growing evidence shows that changes in microbial metabolites, intestinal permeability, and systemic immune activation caused by dysbiosis all lead to NLRP3 inflammasome signaling in microglia, astrocytes, and neurons. This neuroinflammatory response mediated by the inflammasome has been progressively associated with the pathophysiology of autism spectrum disorder (ASD) and stress-related neuropsychiatric diseases, such as anxiety and post-traumatic stress disorder. Gut microbial disturbances facilitate peripheral cytokine release, compromise the blood–brain barrier, induce mitochondrial stress, and generate reactive oxygen species—all of which are crucial upstream activators of NLRP3. The development of interleukin (IL)-1β and IL-18, which depends on inflammasomes, worsens synaptic plasticity, neurotransmitter balance, and control of the hypothalamic–pituitary–adrenal axis. In this review, we integrate novel mechanistic findings that link gut microbiota dysregulation to NLRP3-mediated neuroinflammation, clarify its involvement in ASD and stress susceptibility, and examine treatment approaches targeting microbial modulation and inflammasome suppression. Comprehending this immunometabolic axis may facilitate targeted neuroimmune therapies for neurodevelopmental and stress-related diseases.

Keywords
NOD-like receptor pyrin domain-containing protein 3 inflammasome
Dysbiosis
Autism spectrum disorder
Stress disorder
Neuroinflammation
Microglia
Interleukin-1 beta
Interleukin-18
Funding
None.
Conflict of interest
The author declares no conflict of interest.
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