Mucosal fungi promote gut barrier function and social behavior via Type 17 immunity
Open accessAbstract
Fungal communities (the mycobiota) are an integral part of the gut microbiota, and the disruption of their integrity contributes to local and gut-distal pathologies. Yet, the mechanisms by which intestinal fungi promote homeostasis remain unclear. We characterized the mycobiota biogeography along the gastrointestinal tract and identified a subset of fungi associated with the intestinal mucosa of mice and humans. Mucosa-associated fungi (MAF) reinforced intestinal epithelial function and protected mice against intestinal injury and bacterial infection. Notably, intestinal colonization with a defined consortium of MAF promoted social behavior in mice. The gut-local effects on barrier function were dependent on IL-22 production by CD4+ T helper cells, whereas the effects on social behavior were mediated through IL-17R-dependent signaling in neurons. Thus, the spatial organization of the gut mycobiota is associated with host-protective immunity and epithelial barrier function and might be a driver of the neuroimmune modulation of mouse behavior through complementary Type 17 immune mechanisms.
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In multiple autoimmune disease mouse models, including EAE, autoimmune arthritis, and autoimmune renal disease, microbiota-specific induction of intestinal Th17 cells is associated with worsened autoimmune disease at extra-intestinal sites.
“Indeed, in multiple autoimmune disease mouse models, including EAE, autoimmune arthritis, and autoimmune renal disease, the microbiota-specific induction of intestinal Th17 cells was found to be associated with worsened autoimmune disease at extra-intestinal sites [50–52].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [52]
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Flagged first, then by citations
Research works printed but not linked: 1
- Li XV, Leonardi I, Putzel GG, Semon A, Fiers WD, Kusakabe T, Doron I, Gao IH, Lin W-Y, Gutierrez-Guerrero A, Bialt-DeCelie M, Yang C, Naglik JR, Hube B, Scherl E, Iliev ID, 2022. Strain-level diversity defines host-mycobiota interactions and inflammation in inflammatory bowel disease. Nature in press.
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TH17 cell heterogeneity and its role in tissue inflammation
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Microbiota in inflammatory bowel disease: mechanisms of disease and therapeutic opportunities
Iliev, I. D., Ananthakrishnan, A. N., & Guo, C.-J. (2025) · Nature Reviews Microbiology · doi:10.1038/s41579-025-01163-0 · Cited by 249 · see citing works
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Interleukin-17 as a key player in neuroimmunometabolism
Douglas, A., Stevens, B., & Lynch, L. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00846-3 · Cited by 49 · see citing works
Regulation of microglial physiology by the microbiota
Cook, J., & Prinz, M. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2125739 · Cited by 49 · see citing works
- Authors
- Leonardi, I., Gao, I. H., Lin, W.-Y., Allen, M., Li, X. V., Fiers, W. D., De Celie, M. B., Putzel, G. G., Yantiss, R. K., Johncilla, M., Colak, D., & Iliev, I. D.
- Affiliations
- Cornell University (US)
- Corresponding author
- Iliev, Iliyan D.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2022-03
- Volume
- 185
- Issue
- 5
- Pages
- 831-846.e14
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8897247
- OpenAlex
- W4212813338
- Cited by
- 307
- References
- 109
- Citations by year
- 2026: 50 · 2025: 66 · 2024: 71 · 2023: 78 · 2022: 41
- FWCI
- 20.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 367 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01AI163007, R01DK113136, R01DK121977)
- Burroughs Wellcome Fund
- Irma T. Hirschl Trust
- Leona M. and Harry B. Helmsley Charitable Trust
- Crohn's and Colitis Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Mycorrhizal Fungi and Plant Interactions
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- gut mycobiome, intestinal barrier function, IL-22, social behavior, neuroimmunomodulation, CD4+ T helper cells, intestinal injury, bacterial infection, intestinal epithelium
- MeSH terms
- Gastrointestinal Microbiome, Mycobiome, Animals, Fungi, Intestinal Mucosa, Mucous Membrane, Social Behavior, Immunity, Mucosal, Mice, Receptors, Interleukin-17
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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