Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers
Open accessAbstract
Butyrate, one of the SCFA, promotes the development of the intestinal barrier. However, the molecular mechanisms underlying the butyrate regulation of the intestinal barrier are unknown. To test the hypothesis that the effect of butyrate on the intestinal barrier is mediated by the regulation of the assembly of tight junctions involving the activation of the AMP-activated protein kinase (AMPK), we determined the effect of butyrate on the intestinal barrier by measuring the transepithelial electrical resistance (TER) and inulin permeability in a Caco-2 cell monolayer model. We further used a calcium switch assay to study the assembly of epithelial tight junctions and determined the effect of butyrate on the assembly of epithelial tight junctions and AMPK activity. We demonstrated that the butyrate treatment increased AMPK activity and accelerated the assembly of tight junctions as shown by the reorganization of tight junction proteins, as well as the development of TER. AMPK activity was also upregulated by butyrate during calcium switch-induced tight junction assembly. Compound C, a specific AMPK inhibitor, inhibited the butyrate-induced activation of AMPK. The facilitating effect of butyrate on the increases in TER in standard culture media, as well as after calcium switch, was abolished by compound C. We conclude that butyrate enhances the intestinal barrier by regulating the assembly of tight junctions. This dynamic process is mediated by the activation of AMPK. These results suggest an intriguing link between SCFA and the intracellular energy sensor for the development of the intestinal barrier.
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Short-chain fatty acids maintain gut health by promoting intestinal barrier integrity, mucus production, and supporting a tolerogenic response over inflammation.
“SCFAs maintain gut health by promoting intestinal barrier integrity, mucus production, and supporting a tolerogenic response over inflammation (49, 50, 98, 99).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [50]
Butyrate is shown to enhance intestinal barrier function by reinforcing tight junction assembly, which in theory should prevent endotoxin translocation and reduce circulating inflammation.
“butyrate is shown to enhance intestinal barrier function by reinforcing tight junction assembly [96], which, in theory, should prevent endotoxin translocation and reduce circulating inflammation [97].”
From Gut Microbiota Contribute to Age-Related Changes in Skeletal Muscle Size, Composition, and Function: Biological Basis for a Gut-Muscle Axis (2018) · cites this paper as [96]
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- Authors
- Peng, L., Li, Z.-R., Green, R. S., Holzmanr, I. R., & Lin, J.
- Affiliations
- Tongji University (CN)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Lin, Jing
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 139
- Issue
- 9
- Pages
- 1619-1625
- ISSN
- 0022-3166 (ISSN-L)
- PMC
- PMC2728689
- OpenAlex
- W2155770880
- Cited by
- 2,130
- References
- 46
- Citations by year
- 2026: 292 · 2025: 211 · 2024: 209 · 2023: 226 · 2022: 239 · 2021: 231 · 2020: 183 · 2019: 129 · 2018: 113 · 2017: 83 · 2016: 65 · 2015: 41 · 2014: 26 · 2013: 29 · 2012: 27
- FWCI
- 6.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NIH R03)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- butyrate, short-chain fatty acids, intestinal barrier, tight junction assembly, AMPK, Caco-2 cell monolayers, transepithelial electrical resistance, inulin permeability, tight junction proteins, energy sensing, compound C
- MeSH terms
- Butyrates, Epithelium, Humans, Intestinal Mucosa, Inulin, Membrane Proteins, Permeability, Phosphorylation, Up-Regulation, Electric Impedance, Caco-2 Cells, Tight Junctions, Protein Kinase Inhibitors, AMP-Activated Protein Kinases
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