For years, research into inflammatory bowel disease has focused heavily on bacteria living in the intestine. But bacteria are only part of the microbial community. Fungi also inhabit the digestive tract, and growing evidence suggests that, in some people with Crohn’s disease or ulcerative colitis, an imbalance in these organisms may help sustain intestinal inflammation.
A study published in Nature Medicine in September 2026 has now provided early clinical evidence that reducing an overgrowth of the fungus Candida albicans may reshape the broader gut microbiome and coincide with improvement in inflammatory bowel disease, or IBD. The findings do not establish antifungal drugs as a treatment for IBD, but they raise an intriguing possibility: for a subgroup of patients, inflammation may be influenced not only by the immune system itself, but also by the microbial ecosystem the immune system is responding to.
The Often-Overlooked Fungal Side of the Microbiome
The intestinal microbiome is commonly described as a community of bacteria, yet the intestine also contains fungi, viruses and other microorganisms that continuously interact with one another and with the immune system. The fungal portion of this ecosystem, known as the mycobiome, has increasingly been linked to IBD.
Earlier studies found altered fungal communities in people with Crohn’s disease and ulcerative colitis. Particular attention has been drawn to Candida albicans, a yeast that normally lives harmlessly on mucosal surfaces but can behave differently under certain conditions. Some strains can change shape, invade mucosal surfaces and produce candidalysin, a peptide toxin capable of damaging epithelial cells and stimulating inflammatory immune responses.
The relationship appears to depend on more than simply whether Candida is present. Different strains may interact with the immune system very differently. In a 2022 Nature study, C. albicans strains with greater capacity to damage immune cells were associated with features of intestinal inflammation, and candidalysin was implicated in driving inflammatory responses.
The immune system normally helps keep this fungal population under control. Secretory immunoglobulin A, or IgA, coats microorganisms at mucosal surfaces and appears to recognize fungal structures associated with more aggressive forms of Candida. In Crohn’s disease, some of these antifungal IgA responses have been found to be diminished, suggesting that the usual relationship between fungi and mucosal immunity may become disturbed.
A Clue Hidden in the Mouth
The 2026 study began with an unusual observation. Among some people with IBD and mild oral thrush, genetically related C. albicans strains were found in both the mouth and the gastrointestinal tract. The mouth, in other words, appeared to offer a window into what was happening farther down the digestive system.
Fifty-three patients with mild-to-moderate Crohn’s disease or ulcerative colitis who also had oral thrush were studied. Eighteen received nystatin, an antifungal medication used as a mouth rinse and largely restricted to the oral cavity. Thirty-five received fluconazole, a systemic antifungal that can reach both the mouth and gastrointestinal tract. Both approaches could treat oral thrush, but their effects inside the intestine were markedly different.
This distinction created a useful natural experiment. If eliminating Candida from the mouth alone improved the intestinal microbiome, nystatin might be expected to produce similar changes. Instead, broad changes were seen primarily when intestinal fungal burden was reduced with fluconazole.
When Candida Declined, Bacteria Changed Too
After fluconazole treatment, intestinal Candida levels fell substantially and the fungal community shifted. But the changes did not stop with fungi. Bacterial diversity increased, and bacteria capable of producing short-chain fatty acids expanded. These compounds, particularly butyrate, are produced when certain intestinal bacteria ferment dietary fiber and are involved in nourishing colon cells, maintaining the intestinal barrier and regulating immune responses.
This is where the study becomes especially interesting. The gut does not appear to operate as separate fungal and bacterial ecosystems. Instead, fungi and bacteria compete, cooperate and alter one another's environment. When one group expands excessively, other organisms may be displaced. Reducing an overabundant fungus may therefore allow beneficial bacterial communities to re-establish themselves.
The researchers described corresponding changes in microbial metabolites as well. Metabolic patterns associated with healthier intestinal function increased after fluconazole treatment, including pathways involving fatty acids and bile acids. The findings suggest that changing one part of the microbiome may reverberate throughout the ecosystem, altering not only which microorganisms are present but also the chemicals they produce.
Microbiome Changes Were Accompanied by Symptom Improvement
The microbial changes were accompanied by encouraging clinical observations. Disease activity generally improved more often among patients who received fluconazole than among those treated only with oral nystatin, and the probability of disease progression during the eight-week follow-up was lower in the fluconazole group.
That association is important, but it must be interpreted cautiously. The study was prospective and observational, not a randomized, placebo-controlled clinical trial. Only 53 patients were included, and all had both IBD and oral thrush. The participants were also continuing their usual IBD treatment, making it difficult to determine precisely how much of the clinical improvement was caused by antifungal therapy itself. The authors therefore describe the results as a framework for future testing rather than evidence that fluconazole should routinely be added to IBD treatment.
There is also evidence that the idea deserves further investigation. An earlier randomized placebo-controlled trial in patients with active ulcerative colitis and detectable stool Candida had already examined oral fluconazole, suggesting that fungal targeting in carefully selected patients may warrant additional study.
The Mouth Could Become a Microbial Biomarker
Perhaps one of the most practical findings is the proposed connection between oral and intestinal Candida. Sequencing indicated that fungal strains from the mouth and intestine were often closely related within the same patient.
If this observation is confirmed in larger studies, a cheek swab could eventually help identify patients whose intestinal disease is accompanied by Candida overgrowth. Rather than prescribing an antifungal drug broadly to everyone with IBD, treatment could potentially be directed toward a biologically defined subgroup.
Such a strategy would fit a larger movement toward precision medicine in IBD. Crohn’s disease and ulcerative colitis are unlikely to arise from a single inflammatory pathway. Genetics, epithelial barrier function, immune responses, diet, bacteria and fungi may contribute differently from one patient to another. A microbial marker could help distinguish patients in whom fungal dysbiosis is actually relevant from those in whom it is not.
Why Antifungals Are Not Yet an IBD Treatment
The results should not be interpreted as a reason for people with Crohn’s disease or ulcerative colitis to take fluconazole on their own. Systemic antifungal medications can cause adverse effects, interact with other drugs and contribute to antifungal resistance. More importantly, Candida is a normal member of the human microbiome in many healthy people. Simply finding it does not mean that it is causing disease.
The durability of the effect is another open question. Fungi began to return in some patients after treatment was stopped, raising the possibility that changing the microbial ecosystem temporarily may not produce lasting control. Whether repeated treatment would be effective, safe or even desirable remains unknown.
Larger multicenter, randomized placebo-controlled trials will therefore be needed to determine whether suppressing intestinal Candida actually causes sustained improvement in IBD, which patients are most likely to benefit and whether microbiome-directed therapy could eventually reduce dependence on corticosteroids or other immunosuppressive treatments.
Treating the Ecosystem, Not Just the Immune Response
The broader message may extend beyond fluconazole. Modern IBD therapies have become increasingly sophisticated at blocking inflammatory pathways, yet inflammation occurs within an intestinal ecosystem containing trillions of interacting microorganisms. In some patients, part of the inflammatory signal may originate from that ecosystem itself.
The 2026 study suggests that altering fungi can produce changes across bacterial communities, microbial metabolites and clinical disease activity. Rather than viewing bacteria, fungi and the immune system as separate players, IBD may increasingly be understood as a disorder involving communication among all three.
The most interesting possibility is therefore not that an old antifungal medication will become a universal treatment for inflammatory bowel disease. It is that fungal biology may help reveal why seemingly similar patients have very different forms of the same disease. If those differences can be measured, treatment might eventually be directed not simply at suppressing inflammation, but at correcting the microbial disturbances helping to sustain it.
Reference
1. Pan X, Conroy A, Ngima TS, et al. Antifungal therapy improves microbiome dynamics in inflammatory bowel disease. Nat Med. Published online September 1, 2026. doi:10.1038/s41591-026-04616-y
2. Li XV, Leonardi I, Putzel GG, et al. Immune regulation by fungal strain diversity in inflammatory bowel disease. Nature. 2022;603(7902):672-678. doi:10.1038/s41586-022-04502-w
3. Doron I, Mesko M, Li XV, et al. Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn's disease. Nat Microbiol. 2021;6(12):1493-1504. doi:10.1038/s41564-021-00983-z
4. Sokol H, Leducq V, Aschard H, et al. Fungal microbiota dysbiosis in IBD. Gut. 2017;66(6):1039-1048. doi:10.1136/gutjnl-2015-310746
5. Jena A, Dutta U, Shah J, et al. Oral Fluconazole Therapy in Patients With Active Ulcerative Colitis Who Have Detectable Candida in the Stool : A Double-Blind Randomized Placebo-controlled Trial. J Clin Gastroenterol. 2022;56(8):705-711. doi:10.1097/MCG.0000000000001609
