Genetic and phenotypic diversity of fecal Candida albicans strains in irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) is a common disorder characterized by chronic abdominal pain and changes in bowel movements. Visceral hypersensitivity is thought to be responsible for pain complaints in a subset of patients. In an IBS-like animal model, visceral hypersensitivity was triggered by intestinal fungi, and lower mycobiota α-diversity in IBS patients was accompanied by a shift toward increased presence of Candida albicans and Saccharomyces cerevisiae. Yet, this shift was observed in hypersensitive as well as normosensitive patients and diversity did not differ between IBS subgroups. The latter suggests that, when a patient changes from hyper- to normosensitivity, the relevance of intestinal fungi is not necessarily reflected in compositional mycobiota changes. We now confirmed this notion by performing ITS1 sequencing on an existing longitudinal set of fecal samples. Since ITS1 methodology does not recognize variations within species, we next focused on heterogeneity within cultured healthy volunteer and IBS-derived C. albicans strains. We observed inter- and intra-individual genomic variation and partial clustering of strains from hypersensitive patients. Phenotyping showed differences related to growth, yeast-to-hyphae morphogenesis and gene expression, specifically of the gene encoding fungal toxin candidalysin. Our investigations emphasize the need for strain-specific cause-and-effect studies within the realm of IBS research.

Candidalysin: Connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties

“…While this was not shown to be explicitly NLRP3 dependent, it is reasonable to speculate given that one study has demonstrated hyperactivation of NLRP3 in Crohn’s Disease patients (60%) as compared to healthy controls (28.6%) ( 64 ). Similar to vaginal isolates, GI isolates exhibit phenotypic heterogeneity with respect to growth, yeast-to-hypha transition, and ECE1 expression, underscoring that isolate-to-isolate diversity impacts disease outcome ( 65 ). Therefore, CL may push or exacerbate GI dysbiosis and precipitate immunopathogenesis of the human gut.…”

Candida spp. in Human Intestinal Health and Disease: More than a Gut Feeling

“…Similar to the lack of taxonomic classification or identification, differences between fungal strains within individuals cannot be detected using ITS metabarcoding nor by Sanger sequencing. This sub-species variability may be important in disease as previously described for IBD and IBS [ 22 , 24 , 28 ]. More specialized techniques such as Amplified Fragment Length Polymorphism fingerprinting (AFLP), Random Amplified Polymorphic DNA (RAPD), microsatellite typing or whole genome sequencing (WGS) are needed to properly describe these variations.…”

“…Phenotypic characteristics including adherence to epithelial cells, enzyme release, and gene expression alterations during yeast-to-hyphae transition ( ECE1, ALS3 , and SAP2 ) were observed between the strains. No clear-cut association was observed between virulence-associated traits and visceral sensitivity status, in part due to small group sized in this study [ 24 ]. Further research should indicate whether the virulent capacity of C. albicans strains indeed contribute to altered sensitivity status and abdominal pain in IBS.…”

“…However, since previous research had indicated a fungal contribution to visceral hypersensitivity [ 17 ], it was hypothesized that functional capacities of the fungal community may contribute to altered colorectal sensitivity. The most frequently cultured species was again C. albicans , and isolates showed genetic variation within and between individuals [ 24 ]. Interestingly, isolates of hypersensitive IBS patients partially clustered together.…”

LiveMalasseziastrains isolated from the mucosa of patients with ulcerative colitis

“…For example, S. cerevisiae and C. albicans isolated from the feces of patients with CD displayed different in vitro and in vivo immune responses 68 . Moreover, C. albicans strains isolated from patients with irritable bowel syndrome (IBS) displayed phenotypic diversities, and genotypic analysis revealed that the strains isolated from the gut of hypersensitive IBS patients partially clustered together 69 . However, whether the colonization of a specific body site is associated with genotypic and phenotypic diversities, including virulence, remains unclear.…”