Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22
Open accessAbstract
Endogenous tryptophan (Trp) metabolites have an important role in mammalian gut immune homeostasis, yet the potential contribution of Trp metabolites from resident microbiota has never been addressed experimentally. Here, we describe a metabolic pathway whereby Trp metabolites from the microbiota balance mucosal reactivity in mice. Switching from sugar to Trp as an energy source (e.g., under conditions of unrestricted Trp availability), highly adaptive lactobacilli are expanded and produce an aryl hydrocarbon receptor (AhR) ligand-indole-3-aldehyde-that contributes to AhR-dependent Il22 transcription. The resulting IL-22-dependent balanced mucosal response allows for survival of mixed microbial communities yet provides colonization resistance to the fungus Candida albicans and mucosal protection from inflammation. Thus, the microbiota-AhR axis might represent an important strategy pursued by coevolutive commensalism for fine tuning host mucosal reactivity contingent on Trp catabolism.
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In Ido1−/− mice, bacteria that metabolize dietary tryptophan to indole derivatives gain a selective advantage because tryptophan availability is increased.
“In Ido1−/− mice, which cannot produce the endogenous AhR ligand l-kynurenine, bacteria that are able to metabolize dietary tryptophan and produce indole derivatives gain a selective advantage due to the increased availability of tryptophan.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Zelante et al., 2013
Indole derivatives produced by these bacteria can compensate for the lack of endogenous AhR ligands, reflecting a mutualistic balance between microbiome and host.
“Indole derivatives produced by these bacteria can then compensate for the lack of endogenously produced AhR ligands, reflecting an interesting mutualistic balance between the needs of microbiome and host (Zelante et al., 2013).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Zelante et al., 2013
Activation of AhR by tryptophan metabolites promotes immune cell maturation and decreased pathogen colonization.
“Activation of AhR by tryptophan metabolites promotes immune cell maturation and decreased pathogen colonization.89”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [89]
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- Authors
- Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., Zecchi, R., D’Angelo, C., Massi-Benedetti, C., Fallarino, F., Carvalho, A., Puccetti, P., & Romani, L.
- Affiliations
- University of Perugia (IT)
- University of Florence (IT)
- Corresponding author
- Romani, Luigina
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 39
- Issue
- 2
- Pages
- 372-385
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2044216294
- Cited by
- 2,614
- References
- 56
- Citations by year
- 2026: 385 · 2025: 285 · 2024: 279 · 2023: 237 · 2022: 268 · 2021: 248 · 2020: 249 · 2019: 179 · 2018: 136 · 2017: 119 · 2016: 100 · 2015: 66 · 2014: 54 · 2013: 4
- FWCI
- 33.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- tryptophan catabolites, gut microbiota, aryl hydrocarbon receptor, indole-3-carboxaldehyde, IL-22, mucosal immunity, lactobacilli, Candida albicans, colonization resistance, commensalism, host-microbe interactions, dietary tryptophan
- MeSH terms
- Interleukin-22, Animals, Candida albicans, Candidiasis, Energy Metabolism, Female, Indoles, Interleukins, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Tryptophan, Mice, SCID, Receptors, Aryl Hydrocarbon, Mice, Knockout, Probiotics, Interleukin-17, Gastrointestinal Tract, Indoleamine-Pyrrole 2,3,-Dioxygenase, Toll-Like Receptor 2, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Limosilactobacillus reuteri, Myeloid Differentiation Factor 88, Metagenome
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