Fungal dysbiosis: immunity and interactions at mucosal barriers

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 pathologic changes in the microbiota, historically termed as ‘dysbiosis’, are at the root of many inflammatory diseases of non-infectious origin. Yet, the importance of dysbiosis in the fungal community— the mycobiota — was only recently acknowledged to have a pathological role as novel findings suggest 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 patterns associated with fungal dysbiosis, and discuss how mucosal immunity has evolved to distinguish fungal infection 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 influence health and disease.

Regulation of inflammation by microbiota interactions with the host

“…Mycobiota diversity increases in the lower gastrointestinal tract, and several genera such as Candida , Saccharomyces , Aspergillus , Cryptococcus , Malassezia , Cladosporium , Galactomyces and Trichosporon have the potential to colonize the intestines 7,42–44 . Fungal-community changes with outgrowth of Candida spp .…”

“…have been documented in people with IBD 43,45–47 . Deficiencies in the receptor Dectin-1 (also known as CLEC7A) and the downstream adaptor protein CARD9 lead to susceptibility to more severe experimental colitis as well as fungal and bacterial dysbiosis 6,7,48 . Clec7a –/– mice colonized with Candida tropicalis show aggravated experimental colitis, whereas the absence of Candida leads to less severe disease 6,49 .…”

“…Fungi and bacteria share similar niches in the intestine, and these communities influence each other. Antibiotic treatment promotes gut Candida col-onization 7,50 , which can have immunological outcomes at distant sites such as the lung 7,51 . Bacteria affect fungal colonization both directly and indirectly.…”

“…Sequencing of 16S-rRNA-encoding genes has identified the constituent bacterial species of the human intestinal microbiota as belonging predominantly to the Bacteroidetes and Firmicutes phyla. Deep sequencing of the internal-transcribed-spacer regions ITS1 and ITS2 of the fungal ribosomal DNA and improved downstream analyses 5,6 have unveiled the presence of rich fungal communities, dubbed the mycobiome, within the mammalian intestinal tract 7 . Sequencing of total DNA, the metagenome, from fecal specimens has enabled systematic studies on the virome and has yielded valuable information about the complex interaction of these commensals with their host.…”

Through the Scope Darkly: The Gut Mycobiome Comes into Focus

“…In other words, less than 0.4% of the microbiome literature accounts for the presence of fungi in commensal microbial communities. But recent studies in mice and humans have highlighted the key role of fungi in intestinal homeostasis and systemic immunity (Iliev et al, 2012; Iliev and Leonardi, 2017; Sokol et al, 2013; Tang et al, 2015; Wang et al, 2016), making it difficult to ignore the contribution of fungi to the global effects of the microbiome in health and disease.…”