Key Points
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The term dysbiosis has been used to describe disruptions of microbial communities that lead to a shift in steady-state composition that is distinct from that induced by infections. Recent work has suggested that, in addition to bacterial dysbiosis, fungal dysbiosis might contribute to the pathology of several immune-mediated conditions of non-infectious origin.
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Fungal dysbiosis is observed in human diseases affecting different barrier surfaces, including the mouth, vagina, skin, lungs and gut.
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The mucosal immune system can respond to changes in fungal communities; several antifungal immunity pathways such as C-type lectin receptors, and the IL-1β and inflammasome pathways, might have a role in sensing these fluctuations.
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The interaction between fungi and the host immune system has mainly been studied in the context of infection. However, fungal communities reside on the barrier surfaces of various mammals and are dynamic and responsive to environmental and pathophysiological changes.
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The mammalian gut is a unique site in which fungal infections are rare but fungal dysbiosis occurs frequently.
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Dysbiosis probably affects all communities of the microbiota, including bacterial and fungal species.
Abstract
Fungi and mammals share a co-evolutionary history and are involved in a complex web of interactions. Studies focused on commensal bacteria suggest that pathological changes in the microbiota, historically known as dysbiosis, are at the root of many inflammatory diseases of non-infectious origin. However, the importance of dysbiosis in the fungal community — the mycobiota — was only recently acknowledged to have a pathological role, as novel findings have suggested that mycobiota disruption can have detrimental effects on host immunity. Fungal dysbiosis and homeostasis are dynamic processes that are probably more common than actual fungal infections, and therefore constantly shape the immune response. In this Review, we summarize specific mycobiota patterns that are associated with fungal dysbiosis, and discuss how mucosal immunity has evolved to distinguish fungal infections from dysbiosis and how it responds to these different conditions. We propose that gut microbiota dysbiosis is a collective feature of complex interactions between prokaryotic and eukaryotic microbial communities that can affect immunity and that can influence health and disease.
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Acknowledgements
The authors would like to thank members of the Iliev laboratory and the New York Host-Mycobiota Group for helpful suggestions related to the manuscript. This work was funded by the US National Institutes of Health (grants DK098310 and AI123819 to I.D.I.), Kenneth Rainin Foundation (Innovator and Breakthrough awards to I.D.I), Swiss National Science Foundation (fellowship P2ZHP3_164850 to I.L.) and support from the Jill Roberts Institute for Research in IBD. The authors apologize to all the contributors to this field whose work could not be cited owing to space limitations.
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Glossary
- Symbiosis
-
An ecological relationship between different species that persistently live in close contact. It includes relationships such as mutualism, parasitism and commensalism.
- Dysbiosis
-
A generalized term indicating changes in the composition of the microbiota that is caused by multiple factors. It can be either a cause or a consequence of disease. The term is undergoing revision in light of recent advances in microbiome science.
- Internal transcribed spacer
-
(ITS). A sequence in the fungal genome positioned between the 18S and 5.8S (ITS1) or the 5.8S and 28S (ITS2) fungal rDNA that is widely used in mycobiome next-generation sequencing. The variability of the ITS regions enables them to be used to classify fungal genera and species.
- Operational taxonomic units
-
(OTUs). Clusters of marker gene sequences (for example, 16S rRNA or internal transcribed spacer) based on sequence similarity used for taxonomy-independent community analysis.
- Richness
-
The number of different species represented in an ecological community.
- Commensalism
-
A relationship between two species through which one organism benefits from the other without affecting it.
- Inflammatory bowel disease
-
(IBD). A relapsing and remitting condition of complex aetiology. It is characterized by inflammation of the lower digestive tract with possible extra-intestinal manifestations. The most common types of IBD are Crohn's disease and ulcerative colitis.
- Alpha diversity
-
A biodiversity measure of the mean species diversity within an individual environmental habitat.
- Onychomycosis
-
A fungal infection of the fingernails or toenails.
- Chromoblastomycosis
-
A chronic localized infection of the skin and subcutaneous tissue caused by pigmented fungi that contain sclerotic bodies.
- Phaeohyphomycosis
-
A heterogeneous group of fungal infections that are characterized by the presence of pigmented fungal cells.
- Deep-seated dermatophytosis
-
A fungal infection of deep keratinized tissue (including skin, hair and claws).
- Secukinumab
-
A human monoclonal antibody that binds to IL-17A and inhibits its functions.
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Iliev, I., Leonardi, I. Fungal dysbiosis: immunity and interactions at mucosal barriers. Nat Rev Immunol 17, 635–646 (2017). https://doi.org/10.1038/nri.2017.55
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DOI: https://doi.org/10.1038/nri.2017.55
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Dysbiosis of the intestinal fungal microbiota increases lung resident group 2 innate lymphoid cells and is associated with enhanced asthma severity in mice and humans
Respiratory Research (2023)
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Candida makes a lasting impression in COVID-19
Nature Immunology (2023)
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The impact of the gut microbiome on extra-intestinal autoimmune diseases
Nature Reviews Immunology (2023)
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Abnormal proliferation of gut mycobiota contributes to the aggravation of Type 2 diabetes
Communications Biology (2023)
