Microbial-derived metabolites induce actin cytoskeletal rearrangement and protect blood-brain barrier function
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The gut microbiota influences host brain function, but the underlying gut-brain axis connections and molecular processes remain unclear. One pathway along this bidirectional communication system involves circulating microbially derived metabolites, such as short-chain fatty acids (SCFAs), which include butyrate and propionate. Brain endothelium is the main interface of communication between circulating signals and the brain, and it constitutes the main component of the blood-brain barrier (BBB). Here, we used a well-established in vitro BBB model treated with physiologically relevant concentrations of butyrate and propionate with and without lipopolysaccharide (LPS) to examine the effects of SCFAs on the actin cytoskeleton and tight junction protein structure. Both SCFAs induced distinct alterations to filamentous actin directionality. SCFAs also increased tight junction protein spikes and protected from LPS-induced tight-junction mis-localization, improved BBB integrity, and modulated mitochondrial network dynamics. These findings identify the actin cytoskeletal dynamics as another target further illuminating how SCFAs can influence BBB physiology.
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Butyrate and propionate improved BBB integrity by regulating the organization of the actin cytoskeleton and increasing the interaction between actin and TJ protein ZO-1.
“butyrate and propionate improved BBB integrity by regulating the organization of the actin cytoskeleton and increasing the interaction between actin and TJ protein ZO-1.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [666]
Butyrate and propionate reversed the LPS-induced reduction in ZO-1 and claudin-5 at the cell-cell junctions and restored the LPS-induced mitochondrial dysfunction.
“butyrate and propionate reversed the LPS-induced reduction in ZO-1 and claudin-5 at the cell–cell junctions and restored the LPS-induced mitochondrial dysfunction.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [666]
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Propionic Acid Impact on Multiple Sclerosis: Evidence and Challenges
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Microbiota-Gut-Brain Axis in Age-Related Neurodegenerative Diseases
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Gut–Brain Crosstalk and the Central Mechanisms of Orofacial Pain
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Microbiome: A Key Regulator of Body-Brain Interactions
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Does the Maternal Gut Microbiome Influence the Outcome of Perinatal Asphyxia?
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Gut Microbes: The Gut Brain Connection
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Microbiome, Exposome, and Cognitive Development: The Known Unknowns
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Self-citationIn vitro models of microbiota-gut-brain axis communication at the blood-brain-barrier interface
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The Human Microbiome—A Physiologic Perspective
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How gut microbiota contribute to neuropsychiatric disorders: evidence from neuroimaging studies
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The role of microbiome in gut-brain-axis dysbiosis causing depression: From mechanisms to treatment
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The Gut Vascular Barrier: Linking the Intestinal Environment with Blood Circulation
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- Authors
- Knox, E. G., Aburto, M. R., Tessier, C., Nagpal, J., Clarke, G., O’Driscoll, C. M., & Cryan, J. F.
- Affiliations
- University College Cork (IE)
- Corresponding author
- Cryan, John F.
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2022-12
- Volume
- 25
- Issue
- 12
- Pages
- 105648
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC9732410
- OpenAlex
- W4309730087
- Cited by
- 97
- References
- 65
- Citations by year
- 2026: 27 · 2025: 31 · 2024: 27 · 2023: 11 · 2022: 1
- FWCI
- 6.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- Science Foundation Ireland (SFI/12/RC/2273-P2)
- European Research Council
- Air Force Office of Scientific Research
- European Office of Aerospace Research and Development
- Irish Research Council
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- gut microbiota, short-chain fatty acids, butyrate, propionate, blood-brain barrier, actin cytoskeleton, tight junctions, lipopolysaccharide, mitochondrial dynamics, gut-brain axis, brain endothelium, blood-brain barrier integrity
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