The gut commensal fungus, Candida parapsilosis, promotes high fat-diet induced obesity in mice

Shanshan Sun,Huanqin Dai,Hantian Li,Kai Wang,Shuyang Zhang,Xiaomin Hu,Li Sun,Shanshan Qiao,Xinyue Zhao,Hongwei Liu,Wei Chen

doi:10.1038/s42003-021-02753-3

Abstract

Gut fungi is known to play many important roles in human health regulations. Herein, we investigate the anti-obesity efficacy of the antifungal antibiotics (amphotericin B, fluconazole and 5-fluorocytosine) in the high fat diet-fed (HFD) mice. Supplementation of amphotericin B or fluconazole in water can effectively inhibit obesity and its related disorders, whereas 5-fluorocytosine exhibit little effects. The gut fungus Candida parapsilosis is identified as a key commensal fungus related to the diet-induced obesity by the culture-dependent method and the inoculation assay with C. parapsilosis in the fungi-free mice. In addition, the increase of free fatty acids in the gut due to the production of fungal lipases from C. parapsilosis is confirmed as one mechanism by which C. parapsilosis promotes obesity. The current study demonstrates the gut C. parapsilosis as a causal fungus for the development of diet-induced obesity in mice and highlights the therapeutic strategy targeting the gut fungi.

Highlights

Gut fungi is known to play many important roles in human health regulations
Amphotericin B or fluconazole suppressed the obesity in high fat diet-fed (HFD) mice
To evaluate the impact of intestinal mycobiota on obesity, amphotericin B, fluconazole, and 5-fluorocytosine dissolved in drinking water with a final concentration of 100 mg L−1, 500 mg L−1, and 1 g L−1 were given to HFD mice

Summary

Introduction

We investigate the anti-obesity efficacy of the antifungal antibiotics (amphotericin B, fluconazole and 5-fluorocytosine) in the high fat diet-fed (HFD) mice. Supplementation of amphotericin B or fluconazole in water can effectively inhibit obesity and its related disorders, whereas 5-fluorocytosine exhibit little effects. The gut fungus Candida parapsilosis is identified as a key commensal fungus related to the diet-induced obesity by the culture-dependent method and the inoculation assay with C. parapsilosis in the fungi-free mice. Growing evidence has revealed the vital roles of gut commensal bacteria in the regulation of chronic inflammation, food intake, and energy and nutrients metabolisms, which are all closely related to obesity. We characterized the anti-obesity efficacy of the antifungal antibiotics amphotericin B (Ampho), fluconazole (Flucz), and 5-fluorocytosine (5-Fc) in high-fat diet (HFD)-induced obese mice.

Methods

Results

Conclusion