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

TITLE=Fungal gut microbiota dysbiosis in systemic lupus erythematosus

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1149311

DOI=10.3389/fmicb.2023.1149311

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>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) (<italic>n</italic> = 23), SLE without LN (<italic>n</italic> = 26) and healthy controls (<italic>n</italic> = 14) enrolled in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School.</p></sec><sec><title>Results</title><p>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 <italic>Rhizopus</italic> and <italic>Malassezia</italic>. The main principal components of the flora between the SLE and LN group were generally consistent. The relative abundance of <italic>Vanrija</italic> in the fecal fungal community was higher in LN group, while the relative abundance of <italic>Fusarium</italic> was higher in SLE group. Moreover, our data revealed superior diagnostic accuracy for SLE with the fungal species (e.g. <italic>Candida</italic>, <italic>Meyerozyma</italic>). Correlations between gut fungi and clinical parameters were identified by Spearman’s correlation analysis. Interestingly, <italic>Aspergillus</italic> in SLE patients was positively correlated with ACR, 24 h proteinuria, proteinuria, anti-dsDNA, ANA, and SLEDAI, while <italic>Rhizopus</italic> was negatively correlated with lymphocytes and Hb. Finally, we successfully cultured the fungi and identified it as <italic>Candida glabrata</italic> by microscopic observation and mass spectrometry.</p></sec><sec><title>Discussion</title><p>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.</p></sec>