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PERSPECTIVE ARTICLE

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome at the crossroads of dysbiosis and disease: A target for microbiome-modulated inflammation

Shishir Singh1 ,  Rajeev Nema2 ,  Monisha Banerjee3 ,  Atar Singh Kushwah4*
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1 Department of Medicine, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America
2 Department of Biosciences, School of Physical and Biological Sciences, Faculty of Science, Technology and Architecture, Manipal University Jaipur, Jaipur, Rajasthan, India
3 Molecular and Human Genetics Laboratory, Department of Zoology, Faculty of Sciences, University of Lucknow, Lucknow, Uttar Pradesh, India
4 Translational Oncology and Women’s Health, Department of Biosciences, School of Physical and Biological Sciences, Faculty of Science, Technology and Architecture, Manipal University Jaipur, Jaipur, Rajasthan, India
GPD, 025180034 https://doi.org/10.36922/GPD025180034
Received: 1 May 2025 | Revised: 24 December 2025 | Accepted: 4 January 2026 | Published online: 22 January 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 NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is a critical regulator of inflammation and innate immunity, linking microbial and environmental signals to inflammatory responses. Dysbiosis, an imbalance in the composition of the microbiota, is increasingly recognized as a key trigger for aberrant NLRP3 activation. Under healthy conditions, NLRP3 protects against pathogens and maintains homeostasis; however, chronic activation driven by dysbiosis promotes low-grade inflammation and contributes to various diseases. In the gut, dysbiosis-induced NLRP3 activation is implicated in inflammatory bowel disease, colorectal cancer, obesity, and metabolic disorders. Beyond the gut, dysbiosis in the vaginal microbiome, oral cavity, and skin can activate the NLRP3 inflammasome, driving conditions, such as bacterial vaginosis, periodontitis, and chronic inflammatory skin diseases. Emerging evidence also links dysbiosis-associated NLRP3 activation to neurodegenerative disorders and autoimmune diseases, where systemic inflammation and microbiome disturbances accelerate disease progression. Understanding the mechanisms by which dysbiosis activates the NLRP3 inflammasome is critical for developing targeted therapeutic strategies. Interventions aimed at restoring microbial balance—such as dietary modification, probiotics, and inflammasome inhibitors—may offer promising approaches to mitigate NLRP3-driven inflammation and improve human health outcomes. This perspective highlights the complex interplay between dysbiosis and NLRP3 activation, with a focus on its role in health and disease and on emerging therapeutic strategies to restore homeostasis.

Graphical abstract
Keywords
NLRP3 inflammasome
Dysbiosis
Chronic inflammation
Microbiota
Immune homeostasis
Therapeutic interventions
Funding
None.
Conflict of interest
Atar Singh Kushwah serves as the Youth Editorial Board Member of this journal but was not involved, directly or indirectly, in the editorial decision-making and peer-review process for this paper. All other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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