Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor
Open accessAbstract
Significance: The gut microbiome comprises trillions of microorganisms that inhabit the mammalian intestines. These microbes regulate many aspects of host physiology, including defense mechanisms against factors that contribute to inflammatory bowel diseases (IBDs). Despite the abundance of the gut microbiota, little is known regarding how these microbes modulate these host processes, including the barrier function of the intestinal epithelium, which controls intestinal permeability associated with IBDs. Here, we discover that three gut microbially produced, small-molecule metabolites, which derive from dietary tryptophan, improve intestinal barrier integrity and protect against inflammation caused by IBDs. Our studies identify a host receptor and downstream targets of the metabolites, which could serve as potential pathways for prophylactic and therapeutic treatments for ameliorating morbidity in IBDs.
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Several indole derivatives, including indole-3-ethanol, indole-3-pyruvate, and indole-3-aldehyde, maintain the integrity of the apical junctional complex and improve intestinal barrier integrity by activating the epithelial AHR.
“Several indole derivatives, including indole-3-ethanol, indole-3-pyruvate, and indole-3-aldehyde, maintain the integrity of the apical junctional complex and improve intestinal barrier integrity by activating the epithelial AHR”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [652]
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“AhR aryl hydrocarbon receptor ASBT apical sodium-dependent bile acid transporter ATP adenosine triphosphate BSH bile salt hydrolase C2/C3/C4 acetate/propionate/butyrate CA cholic acid cAMP cyclic adenosine monophosphate CAR constitutive androstane receptor CaSR calcium-sensing receptor CDCA chenodeoxycholic acid CYP45…”
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- Authors
- Scott, S. A., Fu, J., & Chang, P. V.
- Affiliations
- Cornell University (US)
- Corresponding author
- Chang, Pamela V.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-07-27
- Volume
- 117
- Issue
- 32
- Pages
- 19376-19387
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC7431026
- OpenAlex
- W3045898304
- Cited by
- 696
- References
- 57
- Citations by year
- 2026: 166 · 2025: 134 · 2024: 138 · 2023: 97 · 2022: 91 · 2021: 62 · 2020: 8
- FWCI
- 20.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | National Institutes of Health (R35GM133501)
- Arnold and Mabel Beckman Foundation (BYI)
- 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
- tryptophan metabolites, intestinal barrier, aryl hydrocarbon receptor, inflammatory bowel disease, colitis, indole-3-ethanol, indole-3-carboxaldehyde, gut microbiota, intestinal permeability, apical junctional complex, myosin IIA, ezrin, actin regulation, microbial metabolites
- MeSH terms
- Gastrointestinal Microbiome, Ezrin, Animals, Colitis, Ulcerative, Cytoskeletal Proteins, Disease Models, Animal, Humans, Inflammation, Intestinal Mucosa, Permeability, Tryptophan, Receptors, Aryl Hydrocarbon, Mice, Knockout, Caco-2 Cells, Nonmuscle Myosin Type IIA, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins
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