Perturbation of the Gut Fungal Microbiota in Patients with Newly Diagnosed or Untreated Rheumatoid Arthritis Raw sequence reads

#Project Like bacteria, fungi are important members of the intestinal microbiota. Fungal metabolites may also serve as signaling molecules, especially in immune system pathways, and play a critical role in the development and pathogenesis of host autoimmune diseases. Accumulating evidence suggests that intestinal bacterial communities significantly impact the pathogenesis of rheumatoid arthritis (RA). However, the impact of fungal microbiota in the development of RA has not been thoroughly investigated. Thus, we aimed to examine the fecal fungal communities of patients with RA and establish correlations between the abundance of specific genera and disease phenotypes using high-throughput fungal internal transcribed spacer 2 sequencing. Fecal samples were collected from 41 patients with untreated, newly diagnosed RA (Group RA), 54 patients with untreated undifferentiated arthritis (Group UA), and 71 age-, sex-, and ethnicity-matched healthy controls (Group HC). Comparative analysis of the composition, diversity, and richness of the fecal fungal communities was then conducted. Principal coordinate analysis successfully distinguished the RA fungal communities from the UA and the HC communities, with the prevalence and relative abundance of fungi being higher in the RA communities and lower in the UA communities compared with the HC communities. Overall, the genera Chaetomium, Phialosimplex, Schizothecium, and Mortierella were over-represented in the RA fecal samples, while Aspergillus, Candida, and Wallemia and Fusarium, Penicillium, and Sordariomycetes_unclassified were enriched in the UA and HC samples, respectively. Importantly, we established a fecal microbial index (specific alterations in these discriminatory genera) that could be used to distinguish patients with RA from those belonging to groups UA and HC. Our data revealed a distinct fungal dysbiosis in RA patients, characterized by alterations in biodiversity and composition. The identified discriminatory genera could be used as predictors of RA, suggesting that, in addition to bacteria, fungi may play a role in the pathogenesis of RA. Understanding the role of these discriminatory fungi in the pathological progress of RA merits further multi-center and multi-racial prospective research with supporting studies using animal models.