Ponsioen, C. Y. | bioRxiv Science

bioRxiv2024

Typing of feces-derived Candida albicans strains using a novel seven-locus microsatellite panel reveals associations with yeast phenotype in individuals with inflammatory bowel disease

Inflammatory diseases of the human gastrointestinal tract are affected by the microbes that reside in the mucosal surfaces along this tract. Patients with inflammatory bowel diseases (IBD) have altered bacterial and fungal intestinal compositions, including higher levels of fecal Candida yeasts. Ongoing research indicates that genetic and phenotypic diversity of Candida albicans may be linked with disease severity. In this study, we set out to investigate feces-derived C. albicans strains from individuals with Crohns disease, ulcerative colitis, and healthy volunteers through microsatellite-based genotyping and phenotypic assays. A seven-locus microsatellite panel was applied, of which six loci were newly developed. Combined interpretation of minimum spanning networks and principal component analysis (PCA) led to indications that there is no specific lineage of C. albicans that is associated with IBD, but rather that the three study populations do have distinguishable distributions of genotypes. In addition, phenotypic characterization by means of enzyme release assays revealed trends between genotypes and virulence-related enzyme activity. Furthermore, correlations were observed between the clinical inflammation biomarker fecal calprotectin and serum anti- Saccharomyces cerevisiae antibodies, as well as between lipase activity of feces-derived C. albicans strains and serum 1,3-{beta}-glucan levels. We thus show that microsatellite typing can describe genetic diversity of feces-derived C. albicans strains, and that phenotypic diversity of these strains may indeed correlate with fungal genotype or disease. This study opens further possibilities to investigate fecal fungi in relation to severity of inflammation in IBD or in other (intestinal) diseases.

microbiology↗

bioRxiv2021

Drivers and Determinants of Strain Dynamics Following Faecal Microbiota Transplantation

Faecal microbiota transplantation (FMT) is an efficacious therapeutic intervention, but its clinical mode of action and underlying microbiome dynamics remain poorly understood. Here, we analysed the metagenomes associated with 142 FMTs, in a time series-based meta-study across five disease indications. We quantified strain-level dynamics of 1,089 microbial species based on their pangenome, complemented with 47,548 newly constructed metagenome-assembled genomes. Using subsets of procedural-, host- and microbiome-based variables, LASSO-regularised regression models accurately predicted the colonisation and resilience of donor and recipient microbes, as well as turnover of individual species. Linking this to putative ecological mechanisms, we found these sets of variables to be informative of the underlying processes that shape the post-FMT gut microbiome. Recipient factors and complementarity of donor and recipient microbiomes, encompassing entire communities to individual strains, were the main determinants of individual strain population dynamics, and mostly independent of clinical outcomes. Recipient community state and the degree of residual strain depletion provided a neutral baseline for donor strain colonisation success, in addition to inhibitive priority effects between species and conspecific strains, as well as putatively adaptive processes. Our results suggest promising tunable parameters to enhance donor flora colonisation or recipient flora displacement in clinical practice, towards the development of more targeted and personalised therapies.

microbiology↗