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Microbiota-gut-brain axis in health and disease: Is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communications?
Open accessAbstract
Growing evidence highlights the relevance of microbiota-gut-brain axis in the maintenance of brain homeostasis as well as in the pathophysiology of major neurological and psychiatric disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD) and major depressive disorder (MDD). In particular, changes in gut microbiota can promote enteric and peripheral neurogenic/inflammatory responses, which, in turn, could contribute to neuroinflammation and neurodegeneration in the central nervous system (CNS). Of note, the nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome acts as a key player in both coordinating the host physiology and shaping the peripheral and central immune/inflammatory responses in CNS diseases. In this context, there is pioneering evidence supporting the existence of a microbiota-gut-inflammasome-brain axis, in which enteric bacteria modulate, via NLRP3 signaling, inflammatory pathways that, in turn, contribute to influence brain homeostasis. The present review provides an overview of current knowledge on the role of microbiota-gut-inflammasome-brain axis in the major CNS diseases, including PD, AD, MS, ASD and MDD. In particular, though no direct and causal correlation among altered gut microbiota, NLRP3 activation and brain pathology has been demonstrated and in-depth studies are needed in this setting, our purpose was to pave the way to a novel and pioneering perspective on the pathophysiology of CNS disorders. Our intent was also to highlight and discuss whether alterations of microbiota-gut-inflammasome-brain axis support a holistic view of the pathophysiology of CNS diseases, even though each disorder displays a different clinical picture.
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“The NLRP3 inflammasome has been found to play a critical role in microbiota-mediated intestinal/peripheral inflammation and neuroinflammation in CNS diseases.102”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [102]
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Metadata
- Authors
- Pellegrini, C., Antonioli, L., Calderone, V., Colucci, R., Fornai, M., & Blandizzi, C.
- Affiliations
- University of Pisa (IT)
- University of Padua (IT)
- Corresponding author
- Pellegrini, Carolina
- ORCID
- Venue
- Progress in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 191
- Pages
- 101806
- ISSN
- 0301-0082 (ISSN-L)
- OpenAlex
- W3030165573
- Semantic Scholar
- ee46b61c3026c9ee4aa5dbf489c1581b97fa592a
- Cited by
- 174
- References
- 138
- Citations by year
- 2026: 23 · 2025: 31 · 2024: 33 · 2023: 27 · 2022: 34 · 2021: 20 · 2020: 6
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Progress in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, other-oa)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- microbiota-gut-brain axis, NLRP3 inflammasome, gut microbiota, neuroinflammation, neurodegeneration, Parkinson's disease, Alzheimer's disease, multiple sclerosis, autism spectrum disorder, major depressive disorder, neurogenesis, brain homeostasis, central nervous system disorders
- MeSH terms
- Gastrointestinal Microbiome, NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Mental Disorders, Brain Diseases, Humans, Inflammation, Inflammasomes
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