Candida — Are Yeasts in Control of Your Gut?

Aim of the study: Inflammatory bowel disease is shaped by complex microbial communities, yet the contribution of fungal-bacterial interactions to disease progression remains poorly defined. Here, we identify Cladosporium tenuissimum (C.

Results: Notably, dietary threonine restriction markedly attenuates C. albicans-driven colitis in mice. Together, our findings uncover a cross-kingdom metabolic network that determines C. albicans homeostasis and, in turn, governs intestinal inflammatory outcomes, offering new conceptual and therapeutic avenues for IBD.

Aim of the study: The fungal microbiota (mycobiota) is an integral part of the complex multikingdom microbial community colonizing the mammalian gastrointestinal tract and has an important role in immune regulation1-6.

Results: Among these human-gut-derived isolates, strains with high immune-cell-damaging capacity (HD strains) reflect the disease features of individual patients with ulcerative colitis and aggravated intestinal inflammation in vivo through IL-1β-dependent mechanisms. Niche-specific inflammatory immunity and interleukin-17A-producing T helper cell (TH17 cell) antifungal responses by HD strains in the gut were dependent on the C. albicans-secreted peptide toxin candidalysin during the transition from a benign commensal to a pathobiont state. These findings reveal the strain-specific nature of host-fungal interactions in the human gut and highlight new diagnostic and therapeutic targets for diseases of inflammatory origin.

Aim of the study: The fungus Candida albicans frequently colonizes the human gastrointestinal tract, from which it can disseminate to cause systemic disease. This polymorphic species can transition between growing as single-celled yeast and as multicellular hyphae to adapt to its environment.

Results: Hyphal morphotypes are thus under both positive and negative selective pressures in the gut. Our study further shows that candidalysin has a direct inhibitory effect on bacterial species, including limiting their metabolic output. We therefore propose that C. albicans has evolved hyphal-specific factors, including candidalysin, to better compete with bacterial species in the intestinal niche.

Aim of the study: Pathogenic fungi reside in the intestinal microbiota but rarely cause disease. Little is known about the interactions between fungi and the immune system that promote commensalism.

Results: albicans-associated damage during colitis. Together, our findings show that adaptive immunity suppresses harmful fungal effectors, with benefits to both C. albicans and its host. Thus, IgA uniquely uncouples colonization from pathogenesis in commensal fungi to promote homeostasis.

Aim of the study: The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD.

Results: We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis.

Aim of the study: Candida tropicalis-a prevalent gut commensal fungus in healthy individuals - contributes to intestinal health and disease. However, how commensal C.

Results: Notably, a clinical C. tropicalis strain isolated from patients with candidemia lacked the protective effects against murine colitis observed with the reference strain. Together, our results highlight a novel role for C. tropicalis in resolving intestinal inflammation through the modulation of vitamin B3 metabolism.

Aim of the study: Gut fungal dysbiosis has been implicated in inflammatory bowel disease (IBD), yet strategies for targeting the gut mycobiota in IBD remain unexplored.

Results: Among 53 patients with mild-to-moderate ulcerative colitis or Crohn's disease, fluconazole, but not nystatin, effectively reduced intestinal Candida burden and reshaped gut fungal-community composition. Fluconazole treatment was accompanied by increased bacterial diversity, expansion of short-chain fatty-acid-producing taxa, restoration of anti-inflammatory microbial metabolites and durable shifts in cross-kingdom microbial networks. These microbiome and metabolomic changes coincided with improved disease activity indices and a decreased risk of disease progression over the 8-week follow-up period. These findings demonstrate the feasibility of mycobiome-based patient stratification, provide evidence that targeted antifungal therapy can reshape the intestinal microbiota in IBD and establish a framework for implementing antifungal cotherapy in patients with fungal-associated disease manifestations.

Aim of the study: Candida albicans constitutes part of the normal human gastrointestinal (GI) microbiome(GM). Alterations inthe GM induced by antibiotics may disrupt colonization resistance and promote fungal overgrowth. This review summarizes the effects of antibiotics on GI C. albicans colonization in experimental animal models and humans.

Results: Twenty-six articles met the inclusion criteria, comprising 16 murine and 10 human studies. Across all studies, antibiotics were consistently associated with increased GI C. albicans colonization. The greatest increases were observed with broad-spectrum agents with activity against anaerobic bacteria. Elevated fungal concentrations frequently persisted after treatment discontinuation. Human studies largely reproduced findings from murine models. Despite substantial increases in GI colonization, dissemination beyond the GI tract was uncommon. Available evidence demonstrates that antibiotic-induced disruption of the GM promotes GI overgrowth of C. albicans. Hence, C. albicans concentration can serve as an indicator of antibiotics' impact on the GM. While increased colonization alone rarely results in invasive disease, antibiotic-associated yeast expansion may represent an important step in the pathogenesis of disseminated candidiasis.