Iliyan D. Iliev, PhD is a 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

Iliyan D. Iliev, PhD

Gut fungal dysbiosis has been implicated in

, 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.

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

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

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

Articles

Candida overgrowth in IBD may be mechanistically linked to inflammation via candidalysin-mediated epithelial injury and downstream immune activation, with evidence of oral-to-gut strain transfer. In a prospective observational cohort of 53 patients with mild-to-moderate UC or Crohn disease plus oral thrush, systemic fluconazole—unlike topical nystatin—reduced intestinal Candida burden, increased bacterial diversity, and enriched short-chain fatty acid–producing taxa. Fluconazole use correlated with improved partial Mayo and Harvey–Bradshaw scores and lower 8-week progression risk, warranting randomized, endoscopy-informed validation.

Iliyan D. Iliev, PhD, discusses how fluconazole targets gut Candida to improve disease activity in IBD.

Targeting Gut Candida to Treat IBD, With Iliyan D. Iliev, PhD

Fluconazole treatment was associated with improved disease activity scores in patients with 

 (IBD) and oral thrush, while a topical antifungal used to clear the same infection was not.

The finding comes from a 53-patient prospective observational study at Weill Cornell Medicine, published in Nature Medicine, that compared systemic fluconazole with a nystatin rinse in patients already being treated for mild oral thrush as part of routine IBD care.

Antifungal Therapy Eased IBD Activity, With Iliyan D. Iliev, PhD

Disease Activity Improved With Fluconazole in Both Ulcerative Colitis and Crohn's Disease

Disease activity was tracked using the partial Mayo score in patients with 

 and the Harvey-Bradshaw Index in patients with Crohn's disease. 

Iliyan D. Iliev, PhD, 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, said both groups reported improved scores with fluconazole, alongside a decreased risk of disease progression over the 8-week follow-up period.

Iliev said the team could not obtain colonoscopy or biopsy data in such a short window, so clinical indices were the best available measure. He described the 53-patient cohort as an important first step rather than a conclusive result, noting that a placebo-controlled trial would be needed to confirm any clinical benefit.

A Placebo-Controlled Trial Is Needed Before Antifungal Cotherapy Becomes Standard of Care

"If you use them very long term, some of them can lead to liver toxicity and so on. They can lead to resistance," Iliev said of antifungal drugs, explaining why his team would not recommend extended use even if the approach is validated in a larger trial.

Iliev said the next step is a placebo-controlled study with longer follow-up and colonoscopy data, to determine whether the effect is durable and clinically meaningful. He described treatment aimed at the specific windows when Candida expands, rather than continuous antifungal use, as the more realistic model, with the goal of learning whether short antifungal courses could become standard of care for the subset of patients with IBD who experience fungal overgrowth.

"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," Iliev said, describing the broader balance between commensal fungi and disease. 

He added that fungal and bacterial species also play an important role in normal immune development, beyond their role in IBD.

Editor's Note: Iliev reported no relevant disclosures. 

Pan X, Conroy A, Ngima TS, et al. Antifungal therapy improves microbiome dynamics in inflammatory bowel disease. 

. Published online September 1, 2026. doi:10.1038/s41591-026-04616-y

Antifungal therapy shows potential for IBD patients with candida overgrowth. News release. Weill Cornell Medicine. EurekAlert! September 1, 2026. 

Videos

Fluconazole was linked to improved Mayo and Harvey-Bradshaw scores; Iliev outlines the placebo-controlled trial needed next.

Candida albicans strains isolated from the mouth and the gut of the same patient with

are often genetically related, and some produce a toxin that can trigger intestinal inflammation.

That observation led investigators at Weill Cornell Medicine to test whether clearing oral thrush with a systemic antifungal, rather than a topical one, could also clear Candida from the gut and reshape the broader gut microbiome, according to a prospective observational study published in Nature Medicine.

How Candida Moves From Mouth to Gut in IBD, With Iliyan D. Iliev, PhD

Candida Strains Transfer From the Mouth to the Gut in IBD

"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," Iliyan D. Iliev, PhD, 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, said in an interview with 

Iliev's laboratory had previously shown that some Candida albicans strains produce candidalysin, a toxin that damages epithelial and immune cells and can prompt an inflammatory response mistaken for infection. 

To further investigate, Iliev and colleagues tracked patients with mild-to-moderate 

 or Crohn's disease who had mild oral thrush and were already being treated for it as part of routine care. Of 53 patients, 18 received a swish-and-spit nystatin rinse, a topical antifungal, and 35 received fluconazole, which acts systemically through the gastrointestinal tract. Notably, both groups cleared the oral infection.

Fluconazole, Not Nystatin, Recovers Gut Microbial Diversity

"We started seeing this recovery after we cleaned the intestinal Candida, but not when we cleaned only the oral Candida with nystatin," Iliev said.

Only fluconazole reduced Candida burden in the gut. Iliev said that after fluconazole treatment, gut bacterial diversity began recovering, with species associated with a healthy gut starting to repopulate. Metabolites tied to intestinal healing, including butyrate and select bile acids, also increased. He said the team could not yet determine whether this recovery was a direct effect of removing Candida or a downstream result of reduced inflammation once the fungal burden dropped, a question that later, longer-term studies would need to address.

For more on how these findings could translate to practice, see part 2, where Iliev discusses the study's clinical implications and the trial needed to confirm them.

Weill Cornell investigator Iliyan D. Iliev, PhD, explains why fluconazole, not nystatin, cleared gut Candida in IBD.