A Pilot Clinical Study on Post-Operative Recurrence Provides Biological Clues for a Role of Candida Yeasts and Fluconazole in Crohn's Disease.

Nicolas Salvetat,Boualem Sendid,Jean Frédéric Colombel,Dinah Weissmann,Nadine François,Dominique Deplanque,Patrick Gelé,Pierre Desreumaux,Catherine Cunisse,Severine Loridant,Corinne Gower-Rousseau,Samir Jawhara,Helène Sarter,Jordan Leroy,Rachid Aijjou,Daniel Poulain

doi:10.3390/jof7050324

Abstract

Background and aims: This study prompted by growing evidence of the relationship between the yeast Candida albicans and Crohn’s disease (CD) was intended to assess the effect of a 6-month course of the antifungal fluconazole (FCZ) on post-operative recurrence of CD. Methods: Mycological samples (mouth swabs and stools) and serum samples were collected from 28 CD patients randomized to receive either FCZ (n = 14) or placebo (n = 14) before surgical resection. Serological analysis focused on levels of calprotectin, anti-glycan antibodies, and antibody markers of C. albicans pathogenic transition. Levels of galectin-3 and mannose binding lectin (MBL) involved in C. albicans sensing and inflammation were also measured. Results: 1, 2, 3, and 6 months after surgery, endoscopy revealed recurrence in 5/12 (41.7%) patients in the FCZ group and 5/9 (55.6%) in the placebo group, the small cohort preventing any clinical conclusions. In both groups, surgery was followed by a marked decrease in C. albicans colonization and biomarkers of C. albicans pathogenic transition decreased to non-significant levels. Anti-glycan antibodies also decreased but remained significant for CD. Galectin-3 and calprotectin also decreased. Conversely, MBL levels, which inversely correlated with anti-C. albicans antibodies before surgery, remained stable. Building biostatistical multivariate models to analyze he changes in antibody and lectin levels revealed a significant relationship between C. albicans and CD. Conclusion: Several combinations of biomarkers of adaptive and innate immunity targeting C. albicans were predictive of CD recurrence after surgery, with area under the curves (AUCs) as high as 0.86. FCZ had a positive effect on biomarkers evolution. ClinicalTrials.gov ID: NCT02997059, 19 December 2016. University Hospital Lille, Ministry of Health, France. Effect of Fluconazole on the Levels of Anti-Saccharomyces cerevisiae Antibodies (ASCA) After Surgical Resection for Crohn’s Disease. Multicenter, Randomized, and Controlled in Two Parallel Groups Versus Placebo.

Highlights

The yeast Candida albicans is a frequent commensal of humans that can colonize all segments of the digestive tract and vagina
Quantitative assessment of the fungal load (Figure 2B) showed that there was a global reduction in colonization, which mainly concerned C. albicans, and the gradual appearance of other yeast species, which was more pronounced in patients treated with
This study describes the high rate of C. albicans colonization in Crohn’s disease (CD) patients, with

Summary

Introduction

The yeast Candida albicans is a frequent commensal of humans that can colonize all segments of the digestive tract and vagina. The main risk factors are immunodeficiency related to the primary pathology and the medico-surgical procedures used to manage it, including broad-spectrum antibiotics [1] In these patients, C. albicans undergoes saprophytic-pathogenic transition. Results: 1, 2, 3, and 6 months after surgery, endoscopy revealed recurrence in 5/12 (41.7%) patients in the FCZ group and 5/9 (55.6%) in the placebo group, the small cohort preventing any clinical conclusions. In both groups, surgery was followed by a marked decrease in C. albicans colonization and biomarkers of C. albicans pathogenic transition decreased to non-significant levels.

Methods

Results

Conclusion