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Microbiota-Derived Indole Metabolites Promote Human and Murine Intestinal Homeostasis through Regulation of Interleukin-10 Receptor
Open accessAbstract
Interactions between the gut microbiota and the host are important for health, where dysbiosis has emerged as a likely component of mucosal disease. The specific constituents of the microbiota that contribute to mucosal disease are not well defined. The authors sought to define microbial components that regulate homeostasis within the intestinal mucosa. Using an unbiased, metabolomic profiling approach, a selective depletion of indole and indole-derived metabolites was identified in murine and human colitis. Indole-3-propionic acid (IPA) was selectively diminished in circulating serum from human subjects with active colitis, and IPA served as a biomarker of disease remission. Administration of indole metabolites showed prominent induction of IL-10R1 on cultured intestinal epithelia that was explained by activation of the aryl hydrocarbon receptor. Colonization of germ-free mice with wild-type Escherichia coli, but not E. coli mutants unable to generate indole, induced colonic epithelial IL-10R1. Moreover, oral administration of IPA significantly ameliorated disease in a chemically induced murine colitis model. This work defines a novel role of indole metabolites in anti-inflammatory pathways mediated by epithelial IL-10 signaling and identifies possible avenues for utilizing indoles as novel therapeutics in mucosal disease.
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“Indole-3-propionate has been shown to affect host intestinal inflammation and to be reduced in patients with active colitis (Alexeev et al., 2018).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Alexeev et al., 2018
In the citing paper
“healthy ageing correlates with an increased presence of certain indoles, which are gut bacterial degradation products of tryptophan that mediate immune homeostasis upon binding to aryl hydrocarbon receptors and IL-10 receptors15–17”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [17]
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“indolepropionic acid, a microbial metabolite of tryptophan, maintains intestinal homeostasis and protects from experimental colitis (43).”
From The gut microbiota at the intersection of diet and human health (2018) · cites this paper as [43]
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Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286
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Metadata
- Authors
- Alexeev, E. E., Lanis, J. M., Kao, D. J., Campbell, E. L., Kelly, C. J., Battista, K. D., Gerich, M. E., Jenkins, B. R., Walk, S. T., Kominsky, D. J., & Colgan, S. P.
- Affiliations
- University of Colorado Anschutz (US)
- Queen's University Belfast (GB)
- Montana State University (US)
- Corresponding author
- Kominsky, Douglas J.
- Colgan, Sean P.
- ORCID
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 188
- Issue
- 5
- Pages
- 1183-1194
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC5906738
- OpenAlex
- W2788222993
- Cited by
- 532
- References
- 55
- Citations by year
- 2026: 65 · 2025: 84 · 2024: 76 · 2023: 90 · 2022: 68 · 2021: 74 · 2020: 43 · 2019: 22 · 2018: 8
- FWCI
- 13.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion, cc-by-nc-nd)
- Funders
- NIH (DK1047893, DK50189, DK095491, DK103639, DK103712)
- VA Merit (BX002182)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut microbiota, indole metabolites, indole-3-propionic acid, interleukin-10 receptor, IL-10 signaling, aryl hydrocarbon receptor, intestinal homeostasis, colitis, germ-free mice, Escherichia coli, intestinal epithelium, mucosal disease, anti-inflammatory therapy
- MeSH terms
- Animals, Cell Line, Colitis, Disease Models, Animal, Homeostasis, Humans, Indoles, Intestinal Mucosa, Dextran Sulfate, Mice, Receptors, Interleukin-10, Metabolomics, Microbiota
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