Fluconazole, but not nystatin, effectively reduced intestinal Candida burden and reshaped gut fungal-community composition in IBD patients, accompanied by increased bacterial diversity, expansion of short-chain fatty-acid-producing taxa, restoration of anti-inflammatory microbial metabolites, and improved disease activity indices over an 8-week follow-up period.
Key Findings
Results
Fluconazole (GIFT) but not nystatin (ORNT) effectively reduced intestinal Candida burden in IBD patients.
Study compared oral antifungal therapy (swish-and-spit nystatin; ORNT; n=18) with orogastrointestinal antifungal therapy (fluconazole; GIFT; n=35)
Nystatin is not absorbed systemically and thus acts only locally in the oral cavity, while fluconazole reaches the gastrointestinal tract
Fluconazole reshaped gut fungal-community composition while nystatin did not
The study leveraged the observation that Candida albicans strains are shared between the oral cavity and gut in IBD patients with mild oral thrush
Results
Fluconazole treatment was associated with increased bacterial diversity and expansion of short-chain fatty-acid-producing taxa.
The study included 53 patients with mild-to-moderate ulcerative colitis or Crohn's disease
Changes included expansion of short-chain fatty-acid (SCFA)-producing bacterial taxa following fluconazole treatment
Restoration of anti-inflammatory microbial metabolites was observed in the fluconazole group
Durable shifts in cross-kingdom microbial networks accompanied fluconazole treatment
Results
Fluconazole-associated microbiome and metabolomic changes coincided with improved disease activity indices in IBD patients.
Improvements in disease activity indices were observed over an 8-week follow-up period
Fluconazole treatment was associated with a decreased risk of disease progression
The study population included patients with mild-to-moderate ulcerative colitis or Crohn's disease
Both microbiome changes and clinical improvements were observed in the GIFT (fluconazole) group
Background
Candida albicans strains are shared between the oral cavity and gut in IBD patients with mild oral thrush.
This observation was used as the basis for designing the prospective observational study
Oral thrush is a condition caused by Candida overgrowth
The strain-sharing pattern provided a rationale for targeting oral Candida as a means to address gut fungal dysbiosis
This finding enabled patient stratification based on mycobiome characteristics
Conclusions
The study establishes the feasibility of mycobiome-based patient stratification and a framework for antifungal cotherapy in IBD.
Findings demonstrate that targeted antifungal therapy can reshape the intestinal microbiota in IBD
The study design used oral thrush as a clinical indicator for identifying patients with fungal-associated disease manifestations
The authors establish 'a framework for implementing antifungal cotherapy in patients with fungal-associated disease manifestations'
This represents the first prospective observational study comparing antifungal strategies for targeting gut mycobiota in IBD
Background
Gut fungal dysbiosis has been implicated in IBD, yet strategies for targeting the gut mycobiota in IBD had remained unexplored prior to this study.
The study addresses a gap in IBD management regarding mycobiome-targeted interventions
The prospective observational design compared two antifungal delivery strategies (oral-only vs. orogastrointestinal)
The study enrolled 53 total patients across both treatment arms over an 8-week follow-up
What This Means
This research suggests that treating the fungal component of the gut microbiome—specifically Candida overgrowth—may benefit people with inflammatory bowel disease (IBD). The study followed 53 patients with mild-to-moderate Crohn's disease or ulcerative colitis who also had mild oral thrush (a mouth infection caused by Candida fungus). Researchers noticed that the same Candida strains found in patients' mouths were also present in their guts, suggesting the mouth could be a reservoir for gut infection. They compared two antifungal treatments: nystatin (a swish-and-spit rinse that stays in the mouth) and fluconazole (a pill that travels through the entire digestive system). Only fluconazole successfully reduced Candida levels in the gut and changed the overall makeup of the fungal community there.
When Candida levels dropped with fluconazole treatment, positive changes rippled through the broader gut microbiome. Beneficial bacteria that produce short-chain fatty acids—compounds known to reduce gut inflammation—became more abundant. Anti-inflammatory metabolites were restored, and the complex relationships between different microbial kingdoms (bacteria, fungi, and others) were durably restructured. These biological changes were accompanied by measurable improvements in IBD disease activity scores and a lower risk of disease worsening over the 8-week study period.
This research suggests that some IBD patients—particularly those who also develop oral thrush—may have a fungal-driven component to their disease that could potentially be addressed with targeted antifungal therapy alongside standard IBD treatments. The study also demonstrates that a simple clinical sign (oral thrush) could help doctors identify which IBD patients might benefit from this approach, offering a practical framework for patient selection. While the study is observational and involves a relatively small number of patients, it opens a new avenue for thinking about IBD management that goes beyond targeting bacteria alone.
Pan X, Conroy A, Ngima T, Mesko M, Morzhanaeva O, Li A, et al.. (2026). Antifungal therapy improves microbiome dynamics in inflammatory bowel disease.. Nature medicine. https://doi.org/10.1038/s41591-026-04616-y