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Commensal Bacteria-Dependent Indole Production Enhances Epithelial Barrier Function in the Colon
Open accessAbstract
Microbiota have been shown to have a great influence on functions of intestinal epithelial cells (ECs). The role of indole as a quorum-sensing (QS) molecule mediating intercellular signals in bacteria has been well appreciated. However, it remains unknown whether indole has beneficial effects on maintaining intestinal barriers in vivo. In this study, we analyzed the effect of indole on ECs using a germ free (GF) mouse model. GF mice showed decreased expression of junctional complex molecules in colonic ECs. The feces of specific pathogen-free (SPF) mice contained a high amount of indole; however the amount was significantly decreased in the feces of GF mice by 27-fold. Oral administration of indole-containing capsules resulted in increased expression of both tight junction (TJ)- and adherens junction (AJ)-associated molecules in colonic ECs in GF mice. In accordance with the increased expression of these junctional complex molecules, GF mice given indole-containing capsules showed higher resistance to dextran sodium sulfate (DSS)-induced colitis. A similar protective effect of indole on DSS-induced epithelial damage was also observed in mice bred in SPF conditions. These findings highlight the beneficial role of indole in establishing an epithelial barrier in vivo.
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“Indeed, indole has been demonstrated to affect host intestinal epithelial barrier integrity (Bansal et al., 2010), modulate intestinal inflammation (Lamas et al., 2016) and protect against mortality following chemically-induced colitis (Shimada et al., 2013), as well as positively affect host longevity (Sonowal et al., 2017).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Shimada et al., 2013
In the citing paper
“Importantly, supplementation of indole capsules restored gut barrier integrity by elevating junctional protein expression in GF mice.90”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [90]
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“It was reported that indole levels in fecal samples of germ-free (GF) mice were 27-fold lower compared with conventionally raised mice.90”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [90]
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“TJ and AJ proteins (Cldn7, Ocln, ZO-1, E-cadherin 1) are significantly decreased in GF mice compared with conventionally raised mice.90”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [90]
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Metadata
- Authors
- Shimada, Y., Kinoshita, M., Harada, K., Mizutani, M., Masahata, K., Kayama, H., & Takeda, K.
- Affiliations
- Immunology Frontier Research Center, The University of Osaka (JP)
- Japan Science and Technology Agency (JP)
- The University of Osaka (JP)
- Morishita Jintan (Japan) (JP)
- Corresponding author
- Takeda, Kiyoshi
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-11-20
- Volume
- 8
- Issue
- 11
- Pages
- e80604
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3835565
- OpenAlex
- W2040501063
- Cited by
- 404
- References
- 41
- Citations by year
- 2026: 23 · 2025: 43 · 2024: 50 · 2023: 53 · 2022: 44 · 2021: 47 · 2020: 34 · 2019: 27 · 2018: 24 · 2017: 23 · 2016: 15 · 2015: 15 · 2014: 6
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health, Labour and Welfare
- Japan Society for the Promotion of Science (24390120)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- indole, commensal bacteria, intestinal epithelial barrier, tight junctions, adherens junctions, quorum sensing, germ-free mice, DSS-induced colitis, colonic epithelial cells, gut microbiota, epithelial permeability
- MeSH terms
- Animals, Bacteria, Chromatography, High Pressure Liquid, Colon, Germ-Free Life, Indoles, Intestinal Mucosa, Mice, Tandem Mass Spectrometry, Real-Time Polymerase Chain Reaction
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