Fungal gut microbiota dysbiosis in systemic lupus erythematosus

Ping Yang; Rui Xu; Fei Chen; Shanshan Chen; Adeel Khan; Liang Li; Xiaoshan Zhang; Yanbo Wang; Zhipeng Xu; Han Shen

doi:10.3389/fmicb.2023.1149311

Fungal gut microbiota dysbiosis in systemic lupus erythematosus

Front Microbiol. 2023 Apr 5:14:1149311. doi: 10.3389/fmicb.2023.1149311. eCollection 2023.

Authors

Ping Yang¹, Rui Xu², Fei Chen¹, Shanshan Chen³, Adeel Khan⁴, Liang Li², Xiaoshan Zhang¹, Yanbo Wang², Zhipeng Xu⁵, Han Shen¹

Affiliations

¹ Department of Clinical Laboratory, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
² State Key Laboratory of Pharmaceutical Biotechnology, Department of Physiology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, NJU Advanced Institute of Life Sciences (NAILS), Nanjing University, Nanjing, China.
³ Department of Rheumatology and Immunology, Affiliated Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
⁴ Department of Biotechnology, University of Science and Technology, Bannu, Pakistan.
⁵ Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.

Abstract

Introduction: Despite recent developments in our comprehension of how the gut microbiota and systemic lupus erythematosus (SLE) are related. The mycobiome: which is a small but crucial part of the gut microbiota and is involved in hosts' homeostasis and physiological processes, remained unexplored in SLE.

Methods: We profiled the gut fungal mycobiota based on internal transcribed spacer region 1 (ITS1) sequencing for the gut microbial DNA from the SLE individuals with lupus nephritis (LN) (n = 23), SLE without LN (n = 26) and healthy controls (n = 14) enrolled in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School.

Results: The ITS sequencing generated a total of 4.63 million valid tags which were stratified into 4,488 operational taxonomic units (OTUs) and identified about 13 phyla and 262 genera. Patients with SLE were characterized with unique fungal flora feature. The fungal microbiomes of the three groups displayed distinct beta diversity from each other. Compared with HC group, the abundance of fungal dysbiosis was reflected in a higher ratio of opportunistic fungi in SLE or LN group, as well as the loss of Rhizopus and Malassezia. The main principal components of the flora between the SLE and LN group were generally consistent. The relative abundance of Vanrija in the fecal fungal community was higher in LN group, while the relative abundance of Fusarium was higher in SLE group. Moreover, our data revealed superior diagnostic accuracy for SLE with the fungal species (e.g. Candida, Meyerozyma). Correlations between gut fungi and clinical parameters were identified by Spearman's correlation analysis. Interestingly, Aspergillus in SLE patients was positively correlated with ACR, 24 h proteinuria, proteinuria, anti-dsDNA, ANA, and SLEDAI, while Rhizopus was negatively correlated with lymphocytes and Hb. Finally, we successfully cultured the fungi and identified it as Candida glabrata by microscopic observation and mass spectrometry.

Discussion: We first explored the highly significant gut fungal dysbiosis and ecology in patients with SLE, and demonstrated the applicability of fungal species as SLE diagnostic tools, signifying that the gut fungal mycobiome-host interplay can potentially contribute in disease pathogenesis.

Keywords: ITS; biomarkers; fungal microbiota; lupus nephritis; systemic lupus erythematosus.

Grants and funding

We warmly acknowledge the financial aid provided by Nanjing Drum Tower Hospital Clinical Research Special Fund project (Nos. 2022-LCYJ-PY-36 and 2022-LCYJ-MS-28), Natural Science Foundation of Jiangsu Province (Grant No. BK20211586), Qing Lan Project (Grant No. KY101R202127), and the Health Commission Project of Jiangsu Province (Grant No. Z2021004).