Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin
Open accessAbstract
Significance: Intestinal epithelial barrier dysfunction and dysbiosis are central themes of inflammatory bowel diseases (IBDs). Initial studies revealed that the SCFA butyrate selectively promotes epithelial wound-healing responses. Using unbiased single-cell RNA sequencing approaches, we identified a cluster of actin-associated genes regulated by butyrate. Among these, we showed the selective induction of SYNPO as an intestinal tight junction protein with a central role in epithelial barrier regulation. Studies in vivo revealed that microbiota depletion abolished SYNPO expression that was rescued with butyrate. Analysis of Synpo -deficient mice revealed increased susceptibility to colitis and delayed resolution of disease with increased mucosal permeability. These findings highlight a fundamental contribution of the microbiota to homeostatic intestinal mucosal function through selective regulation of SYNPO.
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The beneficial effects of butyrate supplementation on PD pathologies might be attributed to its potent HDAC inhibitory activity and its ability to promote intestinal barrier and BBB integrity.
“The beneficial effects of butyrate supplementation on PD pathologies might be attributed to its potent HDAC inhibitory activity and its ability to promote intestinal barrier and BBB integrity.336–339”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [338]
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- Authors
- Wang, R. X., Lee, J. S., Campbell, E. L., & Colgan, S. P.
- Affiliations
- University of Colorado Anschutz (US)
- Queen's University Belfast (GB)
- Corresponding author
- Colgan, Sean P.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-05-12
- Volume
- 117
- Issue
- 21
- Pages
- 11648-11657
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC7260972
- OpenAlex
- W3024676649
- Cited by
- 318
- References
- 58
- Citations by year
- 2026: 40 · 2025: 66 · 2024: 62 · 2023: 42 · 2022: 50 · 2021: 52 · 2020: 5
- FWCI
- 12.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion, other-oa)
- Funders
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK1047893, DK50189, DK095491, DK103712, F32DK122741, F30DK120072)
- U.S. Department of Veterans Affairs (Merit Award BX002182)
- HHS | NIH | National Institute of General Medical Sciences (T32GM008497)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- butyrate, gut microbiota, synaptopodin, intestinal epithelial barrier, tight junctions, actin cytoskeleton, intestinal homeostasis, inflammatory bowel disease, colitis, mucosal permeability, epithelial repair, microbiota depletion, single-cell RNA sequencing
- MeSH terms
- Gastrointestinal Microbiome, Animals, Butyrates, Cell Line, Homeostasis, Humans, Intestinal Mucosa, Microfilament Proteins, Mice, Knockout, Tight Junctions
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