Altered gut mycobiome and cross-kingdom microbial interactions in systemic lupus erythematosus - Research findings

Sep 29, 2026

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Systemic lupus erythematosus (SLE) is an autoimmune disorder influenced by host genetics and environmental exposures, including the gut microbiota. This study investigates whether the gut mycobiome, its fungal composition and function, and cross-kingdom interactions contribute to SLE pathology. Fecal metagenomic sequencing of 117 SLE patients and 115 healthy controls identifies fungal taxa and metabolic pathways linked to immune activation, inflammation, and disrupted microbial ecological stability, with improved diagnostic value when combining fungal and bacterial profiles.

LanguageEnglish

CategoryResearch & Report

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Pages13

Reading Time33 min

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Abstract

Background

Methods

Results

Conclusions

Introduction

Wang et al. Journal of Translational Medicine (2026) 24:24 [https://doi.org/10.1186/s12967-025-07423-0](https://doi.org/10.1186/s12967-025-07423-0) Journal of Translational Medicine RESEARCH Open Access Altered gut mycobiome and cross-kingdom microbial interactions in systemic lupus erythematosus Zheng Wang 1†, Yida Xing 1†, Mingxi Xu 1†, Changming Chen2†, Qing Zhu3†, Huixiang Chen4, Yidi Zhang2, Wei Chen3, Jianhua Feng5, Aiqin Zhang6, Renzhen Ma6, Xiaohua Liu6, Shenghui Li4, Qiulong Yan3,6, Guorui Xing4*, Xueming Yao2* and Xiaodan Kong 1* Abstract Background Systemic lupus erythematosus (SLE) is a complex autoimmune disorder shaped by host genetics and environmental exposures, including the gut microbiota. While bacterial dysbiosis in SLE is well characterized, the role of the gut mycobiome and its cross-kingdom interactions remains largely unexplored. Methods Using fecal metagenomic sequencing from 117 SLE patients and 115 healthy controls (HCs), we established a non-redundant fungal genome catalog and revealed significant alterations in fungal composition, function, and cross-kingdom ecology. Results Fungal diversity was increased in SLE, with enrichment of potentially pathogenic taxa such as Candida, Malassezia, and Trichophyton, and depletion of commensal genera such as Pichia. Functional analysis showed expanded biosynthetic and redox capacities in SLE-associated fungi, including enrichment of RiPP-and terpenerelated biosynthetic gene clusters and oxidative stress–related Pfam domains. Several predicted metabolites—such as kynurenine, phenylacetic acid, secondary bile acids, and acylcarnitines—were linked to immune activation and inflammation, suggesting that fungal metabolism may contribute to immune dysregulation. Network analysis revealed sparser and less centralized fungal–bacterial interactions in SLE, indicating disrupted ecological stability and the emergence of fungal taxa as key structural drivers. Integrating fungal and bacterial profiles markedly improved diagnostic performance (AUC = 0 . 934), underscoring the complementary predictive value of the gut mycobiome. In contrast, post-treatment samples showed reduced fungal richness but no major compositional shifts. †Zheng Wang, Yida Xing, Mingxi Xu, Changming Chen and Qing Zhu have contributed equally to this work. *Correspondence: Guorui Xing [2657518@qq.com](2657518@qq.com)[ ](2657518@qq.com)Xueming Yao [yxming19@foxmail.com](yxming19@foxmail.com)[ ](yxming19@foxmail.com)Xiaodan Kong [xiaodankong2008@sina.com](xiaodankong2008@sina.com) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/l](vecommons.org/l)icenses/by-nc-nd/4.0/. Wang et al. Journal of Translational Medicine (2026) 24:24 Page 2 of 13 Conclusions This study provides a comprehensive, multi-dimensional view of the gut mycobiome in SLE, demonstrating its taxonomic, functional, and ecological remodeling. Our findings highlight the

FAQs

What question does the study address about SLE?

It examines the role of the gut mycobiome and fungal cross-kingdom interactions in systemic lupus erythematosus, which had been less explored compared with bacterial dysbiosis.

How was the gut mycobiome investigated?

The study used fecal metagenomic sequencing from 117 SLE patients and 115 healthy controls to build a non-redundant fungal genome catalog and analyze taxonomic, functional, and ecological patterns.

What were the main findings linking fungi to SLE?

SLE showed increased fungal diversity with enrichment of potentially pathogenic fungi and depletion of commensals. Fungal functional changes included expanded biosynthetic and redox capacities, and predicted metabolites were linked to immune activation and inflammation, while fungal–bacterial interaction networks became less centralized.

Sep 29, 2026

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