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Fungal-host interactions and the importance of the gut mycobiome
▶ Iliev ID, Funari VA, Taylor KD, et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 2012;336:1314–17.
Commensal fungi have been largely neglected as a component of the gut microbiome, with most research to date focused on bacteria. In a recent study by Iliev et al, abundant fugal populations were observed in colonic specimens from several animal species, and in human faeces. Using high-throughput sequencing, the authors identified over 100 annotated fungal species in mouse faeces, in addition to over 100 novel and/or unannotated species, illustrating the diversity of the murine gut mycobiome. The sequencing data also revealed that over 97% of fungal sequences in the mouse gut belonged to only 10 fungal species, with the majority of sequences belonging to Candida tropicalis. Dectin-1, a C-type lectin receptor, recognises glucan cell wall components, common to virtually all fungi. Downstream signalling from Dectin-1, which involves CARD9, induces pro-inflammatory cytokine production and T helper 17 responses. In a mouse DSS-induced colitis model, Dectin-1 deficient mice experienced increased susceptibility to colitis with enhanced inflammatory response and increased weight loss. Interestingly, during colitis in the Dectin-1 deficient animals, the proportion of pathogenic fungi increased, while non-pathogenic fungal populations diminished. Furthermore, colonic examination of Dectin-1 deficient colitic mice revealed fungi invading inflamed tissue. When Dectin-1 deficient animals were supplemented with C tropicalis (an opportunistic pathogen), then exposed to DSS, the severity of the ensuing colitis was increased. The severity of colitis was, however, attenuated by fluconazole, suggesting that Dectin-1 deficient mice fail to mount an effective response to fungal pathogens during gut inflammatory insult. Given this finding, Iliev et al proceeded to perform a genetic association study where they observed increased frequency of a polymorphism in CLEC7A (the gene encoding Dectin-1 in humans) in …