---
title: "Fluconazole reduces gut Candida and reshapes the microbiome in IBD with oral thrush"
id: "nature-2-antifungal-therapy-improves-microbiome-dynamics-in-inflammatory-bowel-disease"
canonical_url: "https://medichelpline.com/clinical-feed/nature-2-antifungal-therapy-improves-microbiome-dynamics-in-inflammatory-bowel-disease"
content_type: "clinical_feed_article"
specialty: "Gastroenterology"
source_name: "Nature Medicine"
source_url: "https://www.nature.com/articles/s41591-026-04616-y"
published_at: "2026-09-01T12:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Fluconazole reduces gut Candida and reshapes the microbiome in IBD with oral thrush
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/nature-2-antifungal-therapy-improves-microbiome-dynamics-in-inflammatory-bowel-disease
- **Specialty:** [Gastroenterology](https://medichelpline.com/clinical-feed/gastroenterology.md)
- **Primary Source:** Nature Medicine
- **Source URL:** [Original Journal Publication](https://www.nature.com/articles/s41591-026-04616-y)
- **Published At:** 2026-09-01T12:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This prospective observational study enrolled 53 patients with mild-to-moderate ulcerative colitis or Crohn’s disease who had mild oral thrush, a condition linked to Candida overgrowth. - Patients were assigned to oral nystatin fungal targeting (ORNT; swish-and-spit nystatin; n = 18) or gastrointestinal and oral fluconazole fungal targeting (GIFT; fluconazole; n = 35). - **Fluconazole**, but not **nystatin**, significantly reduced intestinal **Candida** burden and altered overall gut fungal-community composition. - Fluconazole treatment was associated with increased bacterial diversity and expansion of **short-chain-fatty-acid-producing taxa**, notably butyrate producers. - Metabolomics showed restoration of anti-inflammatory microbial metabolites in fluconazole-treated patients and identified metabolite modules linked to specific fungal taxa and treatment types. - Cross-kingdom microbial network analyses revealed durable shifts after fluconazole, indicating altered fungus–bacterium interactions. - Clinical measures improved with fluconazole: disease activity indices improved and the risk of disease progression decreased over an 8-week follow-up period; such benefits were not observed with nystatin. - The study supports feasibility of **mycobiome**-based patient stratification and suggests targeted antifungal cotherapy can reshape the intestinal microbiota in IBD patients with fungal-associated manifestations. - Raw sequencing data are available through NCBI SRA (BioProject PRJNA1449485); supplementary tables provide clinical, sequencing, bacterial abundance, and metabolomics data. Analysis code is available on GitHub and archived on Zenodo. - Additional individual-level clinical data are restricted for privacy and IRB reasons; requests can be directed to the corresponding author under institutional requirements.
## Clinical Analysis & Structured Key Points
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[nature](https://www.nature.com/) 2. [nature medicine](https://www.nature.com/nm) 3. [articles](https://www.nature.com/nm/articles?type=article) 4. article * Article * Published: 01 September 2026 # Antifungal therapy improves microbiome dynamics in inflammatory bowel disease * [Xiangyu Pan](https://www.nature.com/articles/s41591-026-04616-y#auth-Xiangyu-Pan-Aff1-Aff2) [ORCID: orcid.org/0000-0002-2537-6616](https://orcid.org/0000-0002-2537-6616)[1](https://www.nature.com/articles/s41591-026-04616-y#Aff1),[2](https://www.nature.com/articles/s41591-026-04616-y#Aff2), * [Aidan Conroy](https://www.nature.com/articles/s41591-026-04616-y#auth-Aidan-Conroy-Aff1-Aff2) [ORCID: orcid.org/0009-0006-1315-019X](https://orcid.org/0009-0006-1315-019X)[1](https://www.nature.com/articles/s41591-026-04616-y#Aff1),[2](https://www.nature.com/articles/s41591-026-04616-y#Aff2), * [Tsering S. Ngima](https://www.nature.com/articles/s41591-026-04616-y#auth-Tsering_S_-Ngima-Aff1-Aff2)[1](https://www.nature.com/articles/s41591-026-04616-y#Aff1),[2](https://www.nature.com/articles/s41591-026-04616-y#Aff2), * [Marissa Mesko](https://www.nature.com/articles/s41591-026-04616-y#auth-Marissa-Mesko-Aff1-Aff2) [ORCID: orcid.org/0000-0002-4788-8794](https://orcid.org/0000-0002-4788-8794)[1](https://www.nature.com/articles/s41591-026-04616-y#Aff1),[2](https://www.nature.com/articles/s41591-026-04616-y#Aff2), * [Olga Morzhanaeva](https://www.nature.com/articles/s41591-026-04616-y#auth-Olga-Morzhanaeva-Aff1-Aff2)[1](https://www.nature.com/articles/s41591-026-04616-y#Aff1),[2](https://www.nature.com/articles/s41591-026-04616-y#Aff2), * [Aurelia Li](https://www.nature.com/articles/s41591-026-04616-y#auth-Aurelia-Li-Aff1-Aff2)[1](https://www.nature.com/articles/s41591-026-04616-y#Aff1),[2](https://www.nature.com/articles/s41591-026-04616-y#Aff2), * [Jamie Marino](https://www.nature.com/articles/s41591-026-04616-y#auth-Jamie-Marino-Aff3)[3](https://www.nature.com/articles/s41591-026-04616-y#Aff3), * [Lars F. Westblade](https://www.nature.com/articles/s41591-026-04616-y#auth-Lars_F_-Westblade-Aff3)[3](https://www.nature.com/articles/s41591-026-04616-y#Aff3), * [Alexander Grier](https://www.nature.com/articles/s41591-026-04616-y#auth-Alexander-Grier-Aff2)[2](https://www.nature.com/articles/s41591-026-04616-y#Aff2), * [Petra Bacher](https://www.nature.com/articles/s41591-026-04616-y#auth-Petra-Bacher-Aff4-Aff5) [ORCID: orcid.org/0000-0003-4264-6451](https://orcid.org/0000-0003-4264-6451)[4](https://www.nature.com/articles/s41591-026-04616-y#Aff4),[5](https://www.nature.com/articles/s41591-026-04616-y#Aff5), * [Randy S. Longman](https://www.nature.com/articles/s41591-026-04616-y#auth-Randy_S_-Longman-Aff1-Aff2-Aff6-Aff7)[1](https://www.nature.com/articles/s41591-026-04616-y#Aff1),[2](https://www.nature.com/articles/s41591-026-04616-y#Aff2),[6](https://www.nature.com/articles/s41591-026-04616-y#Aff6),[7](https://www.nature.com/articles/s41591-026-04616-y#Aff7), * [Ellen J. Scherl](https://www.nature.com/articles/s41591-026-04616-y#auth-Ellen_J_-Scherl-Aff1-Aff6)[1](https://www.nature.com/articles/s41591-026-04616-y#Aff1),[6](https://www.nature.com/articles/s41591-026-04616-y#Aff6) & * … * [Iliyan D. Iliev](https://www.nature.com/articles/s41591-026-04616-y#auth-Iliyan_D_-Iliev-Aff1-Aff2-Aff3-Aff7-Aff8) [ORCID: orcid.org/0000-0003-0884-9749](https://orcid.org/0000-0003-0884-9749)[1](https://www.nature.com/articles/s41591-026-04616-y#Aff1),[2](https://www.nature.com/articles/s41591-026-04616-y#Aff2),[3](https://www.nature.com/articles/s41591-026-04616-y#Aff3),[7](https://www.nature.com/articles/s41591-026-04616-y#Aff7),[8](https://www.nature.com/articles/s41591-026-04616-y#Aff8) Show authors [_Nature Medicine_](https://www.nature.com/nm) (2026) [Cite this article](https://www.nature.com/articles/s41591-026-04616-y#citeas) [ Save article ](https://www.nature.com/articles/s41591-026-04616-y/save-research?_csrf=XD0yXwU9PvMJBHT9JPsExzFCxOzpnvNB) [ View saved research ](https://www.nature.com/saved-research) ## Abstract Gut fungal dysbiosis has been implicated in inflammatory bowel disease (IBD), yet strategies for targeting the gut mycobiota in IBD remain unexplored. Here we leveraged the observation that _Candida albicans_ strains are shared between the oral cavity and gut in patients with IBD with mild oral thrush, a condition caused by _Candida_ overgrowth, to design a prospective observational study comparing oral antifungal therapy (swish-and-spit nystatin; oral nystatin fungal targeting (ORNT); _n_ = 18) with orogastrointestinal antifungal therapy (fluconazole; gastrointestinal and oral fluconazole fungal targeting (GIFT); _n_ = 35). 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. This is a preview of subscription content, [access via your institution](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41591-026-04616-y) ## Access options [ Access through your institution ](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41591-026-04616-y) Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription 27,99 € / 30 days cancel any time [Learn more](https://shop.nature.com/products/plus/?region=ROW) Subscribe to this journal Receive 12 print issues and online access 251,40 € per year only 20,95 € per issue [Learn more](https://www.nature.com/nm/subscribe) Buy this article * Purchase on SpringerLink * Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout ### Additional access options: * [Log in](https://idp.nature.com/authorize/natureuser?client_id=grover&redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41591-026-04616-y) * [Learn about institutional subscriptions](https://www.springernature.com/gp/librarians/licensing/license-options) * [Read our FAQs](https://support.nature.com/en/support/home) * [Contact customer support](https://www.springernature.com/gp/contact) **Fig. 1: Study design and multi-omics overview of patients with IBD with oral thrush.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41591-026-04616-y/MediaObjects/41591_2026_4616_Fig1_HTML.png) **Fig. 2: Fluconazole, but not nystatin, treatment leads to a decrease in gut _Candida_ and changes in the overall mycobiota composition.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41591-026-04616-y/MediaObjects/41591_2026_4616_Fig2_HTML.png) **Fig. 3: Fluconazole treatment fosters cross-kingdom community changes and the expansion of butyrate-producing bacteria.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41591-026-04616-y/MediaObjects/41591_2026_4616_Fig3_HTML.png) **Fig. 4: Metabolomics analysis of patients with IBD reveals metabolite modules linked to specific fungal taxa and antifungal treatment types.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41591-026-04616-y/MediaObjects/41591_2026_4616_Fig4_HTML.png) **Fig. 5: Fluconazole, but not oral nystatin treatment, is associated with improved disease activity.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41591-026-04616-y/MediaObjects/41591_2026_4616_Fig5_HTML.png) ### Explore related subjects Discover the latest articles and news in related subjects. * [Clinical microbiology](https://www.nature.com/subjects/clinical-microbiology) * [Fungi](https://www.nature.com/subjects/fungi) * [Gastrointestinal diseases](https://www.nature.com/subjects/gastrointestinal-diseases) * [Microbiome](https://www.nature.com/subjects/microbiome) ## Data availability Raw fungal ITS amplicon and shotgun metagenomic sequencing data generated in this study are available through the NCBI Sequence Read Archive under BioProject accession [PRJNA1449485](http://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA1449485). The bacterial abundance table, relative metabolite-expression table, sample information and de-identified clinical characteristics used in the analyses are provided in the accompanying Supplementary Tables. Specifically, clinical characteristics and medication information are provided in Supplementary Table [2](https://www.nature.com/articles/s41591-026-04616-y#MOESM2), sequencing-sample information is provided in Supplementary Table [3](https://www.nature.com/articles/s41591-026-04616-y#MOESM2), metabolomics data are provided in Supplementary Table [8](https://www.nature.com/articles/s41591-026-04616-y#MOESM2) and bacterial abundance data are provided in Supplementary Table [10](https://www.nature.com/articles/s41591-026-04616-y#MOESM2). Additional individual-level clinical information that could potentially allow participant re-identification is not publicly available because of participant privacy and institutional review board restrictions. Requests for access to additional de-identified clinical data may be directed to the corresponding author and will be considered in accordance with the informed consent documents, the study protocol and Weill Cornell Medicine institutional requirements. The _C. albicans_ SC5314 reference genome used for WGS analysis is available from NCBI under accession GCA_000182965.3 ( ). [Source data](https://www.nature.com/articles/s41591-026-04616-y#Sec28) are provided with this paper. ## Code availability The analysis code used for quality control, data processing, statistical analysis and visualization of the fungal ITS, metagenomic, metabolomic and clinical data is publicly available in the GitHub repository ( ). A persistent archived version of the code is available on Zenodo at the version cited in ref. [77](https://www.nature.com/articles/s41591-026-04616-y#ref-CR77 "Pan, X. Antifungal therapy improves microbiome dynamics in inflammatory bowel disease, v1. 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