Cited by 318Gut microbiota and healthInflammatory Bowel DiseaseGastrointestinal motility and disorders

Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin

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Wang, Ruth X., Lee, J. Scott, Campbell, Eric L., Colgan, Sean P.·2020·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.1917597117

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58 of 58 references verified0 citation errors · 0 not checkable

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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”

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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
Published
2020-05-12
Volume
117
Issue
21
Pages
11648-11657
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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