Gut fungal dysbiosis has been implicated in inflammatory bowel disease (IBD), yet strategies for targeting the intestinal mycobiota remain unexplored.¹ Iliyan D. Iliev, PhD, is professor of immunology in medicine and co-director of the microbiome core laboratory at the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. He led a new prospective observational study testing whether clearing intestinal Candida could reshape the gut microbiome and disease activity in patients with IBD and oral thrush.

His laboratory has previously shown some Candida albicans strains produce candidalysin, a toxin damaging epithelial and immune cells, linked to impaired intestinal healing and response to therapy in mouse models and patient association studies.²

Investigators compared a topical nystatin rinse (n = 18) with systemic fluconazole (n = 35) in 53 patients with mild-to-moderate ulcerative colitis or Crohn disease and oral thrush treated as part of routine care.¹ Fluconazole, but not nystatin, reduced intestinal Candida burden, increased bacterial diversity, and expanded short-chain fatty acid-producing taxa in the gut.¹ Fluconazole was also associated with improved disease activity indices, measured by the partial Mayo score and Harvey-Bradshaw Index, and a decreased risk of disease progression over 8 weeks.¹

"These results highlight the potential of microbiome-based approaches to restore a balanced microbial community in the gut," said Iliev.³ The study was not randomized or placebo-controlled, and a placebo-controlled trial with longer follow-up and endoscopic data is needed to confirm the findings. In the following interview, Iliyan D. Iliev, PhD, discusses the mechanism linking Candida to intestinal inflammation, the disease activity findings, and the trial needed to confirm antifungal cotherapy in IBD.

Q&A: Fluconazole, Candida, and the Gut Microbiome in IBD

HCPLive: What were you and your co-investigators trying to understand about the gut microbiome in patients with IBD?

Iliyan Iliev, PhD: I'm Iliyan Iliev, and I'm a professor of immunology at Weill Cornell Medical College. We are very interested in the mucosal immune response in the intestines, and we have been working for many years on an interesting part of the intestinal microbiota, the mycobiome, or the fungal communities.

This became very relevant in the context of inflammatory bowel disease because we observed in our patients an expansion of specific fungal species, particularly Candida albicans. Other groups have also shown other members of the mycobiome expanding in the intestines of these patients. We started asking what those species are doing there, and whether there is anything causative happening in the intestine. We studied the immune response and different mediators, and what turned out, in a nutshell, is that those species of Candida albicans are transferred. They are very common in our community, they live in our intestines, and they expand in those patients.

Some of those strains have the ability to produce a toxin called candidalysin, and it drills holes in the epithelial cells and in other inflammatory immune cell populations. What that leads to, we found, is that those cells start producing inflammatory mediators, thinking an infection is happening, and they try to fight the microbe, which leads to increased inflammation. We found this in different mouse models, and we also did association studies in patients showing it actually influences intestinal healing and sometimes even the response to therapy. That study took a long time because the design was very important. We had enough evidence to look at how the treatment would affect the patient population, but not enough to design a placebo-controlled clinical trial. So we explored more what was happening in those patients, and we saw that some of them developed mild candidiasis in their mouth, called oral thrush. We started looking into it more deeply, and it became something very interesting. We started tracking those strains. We have technologies in the lab that can isolate strains from the gut and from the oral mucosa and see if they are the same, and it turned out they are. This brought the idea that some of those strains are transferring from the oral mucosa to the gut, and we know they produce that toxin. So what will happen if we target them?

We designed this study to target Candida in both situations. The patients receive antifungals to control the thrush, and it happens that they are IBD patients. Some of them are treated with nystatin, so they wash their mouth and clear the Candida with nystatin twice a day for two weeks. They clear Candida in their mouth. But what we found is they don't clear it in the gut. Once it seeds the gut, it stays there. The other patients are prescribed fluconazole, which also has a systemic effect. It clears Candida in the oral cavity, and we found it also clears Candida in the gut. So we had two groups of patients we could follow. We followed them for 8 weeks, and in the fluconazole group, where Candida was cleared in both sites, we started seeing a recovery of the microbiome in the gut. In IBD, the diversity of the healthy gut community drops, but after fluconazole treatment, the community started recovering its diversity. Species associated with a healthy gut also started repopulating the gut.

Most importantly, they started producing metabolites known to be important for intestinal healing, such as butyrate. We also looked at some bile acids. We started seeing this recovery after we cleaned the intestinal Candida, but not when we cleaned only the oral Candida with nystatin. This brought us to the conclusion that removing the Candida species that are expanding can lead to some recovery. We cannot tell if it is indirect, meaning you clean the Candida, inflammation subsides, and that is why you have the bacterial recovery. Since this was a short study, only 8 weeks, there is no standard of care that would perform colonoscopy twice in that period, before and after. So we did not have that data, but we had the clinical scores.

We had patients with ulcerative colitis, using the Mayo score, and patients with Crohn disease, using the Harvey-Bradshaw Index, and in both situations we saw clinical improvement. This brought us to the hypothesis that removing the Candida species producing the toxin may lead to a better situation, where you slightly recover from the inflammatory effect of the strains.

HCPLive: What do the disease activity improvements show, and what are the clinical implications?

Iliyan Iliev, PhD: The disease activity is an interesting angle. Again, we didn't have colonoscopy or biopsies that could be taken in such a short time, so the disease activity was probably the best direction we could go. What we saw in both ulcerative colitis and Crohn disease patients is they reported improvement, so improved disease activity, when they were treated with fluconazole, which removes Candida in the oral cavity and in the gut.

This brought the hypothesis that this type of treatment is the one that leads to some benefits. Of course, to have something conclusive, it has to be a placebo-controlled study, and we probably need other angles that will assess, in the long term, whether the patients can be evaluated again in six months or so, and collect colonoscopy data as well. Then we will have a good idea if this is a long-term effect and if it's clinically meaningful. But for that, it has to be a placebo-controlled study. However, in a situation where you start something new, this is the first step, and it's very important to have that first step. It's 53 patients that we could assess here.

HCPLive: What would need to happen before targeted antifungal therapy could become part of how clinicians manage IBD?

Iliyan Iliev, PhD: I feel the next step is, of course, a placebo-controlled clinical trial. Antifungal drugs, if you use them very long term, can lead to liver toxicity and so on. They can lead to resistance. So it's not something we would recommend using, or even test that way, to use it for a very long term.

But in those windows where you have this Candida expansion, that's where we will be targeting. It will be short-term treatment, where we show here it's actually effective, and we do it in a setting where we have the answer of whether this could be a standard of care one day for this subpopulation of patients that experience overgrowth.

HCPLive: Was there anything else you wanted to highlight or add about the study?

Iliyan Iliev, PhD: It's something we have been working on for many years. Mechanistically, it's very interesting because we're learning more and more that fungal species living on our body can do a lot to our normal physiology, but there is a very fine line. People call it dysbiosis. I would call it expansion of those populations.

They find an environment where they will actually grow uncontrollably, and then the immune system reacts to that. It sees there is this growth, and it tries to compensate, and that's where we have these more pathological situations. But as commensals, it's very interesting to study how fungal species and also some bacterial species have an important role in immune system development and in our health overall.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.

References

1. Pan X, Conroy A, Ngima TS, et al. Antifungal therapy improves microbiome dynamics in inflammatory bowel disease. Nat Med. 2026;32(9):3385-3395. 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. Weill Cornell Medicine. Antifungal therapy shows potential for IBD patients with candida overgrowth. Published September 1, 2026. Accessed September 23, 2026. https://www.eurekalert.org/news-releases/1142314