ABSTRACT
Background The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free mice.
Results Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to germ free (GF) C57BL/6 mice caused GF mice to develop a series of lupus-like phenotyptic features, which including an increased serum autoimmune antibodies, and imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants.
Conclusions Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- ACR
- American College of Rheumatology
- Anti-dsDNA
- Anti-double stranded DNA
- ANA
- anti-nuclear antibodies
- DEGs
- Differential expression of genes
- ELISA
- Enzyme-linked immunosorbent assay
- FMT
- Fecal microbiota transplantation
- GC
- Germinal center
- GF
- Germ free
- GO
- Gene ontology
- H4R
- histamine H4 receptor
- ILAS
- Institute of Laboratory Animal Sciences
- IBD
- Inflammatory bowel disease
- LDA
- linear discriminant analysis
- LEfSe
- LDA Effect Size
- IRFs
- IFN regulatory factors
- LN
- Lupus nephritis
- LP
- Lamina propria
- MRL/lpr
- MRL/Mp-Fas lpr mouse
- NGS
- Next-generation sequencing
- OTUs
- Operational taxonomic unit
- PBS
- Phosphate-buffered saline solution
- PBs
- Plasma blast cells
- PCA
- Principal component analysis
- PCs
- Plasma cells
- qRT-PCR
- quantitative real-time PCR
- RA
- Rheumatoid arthritis
- SLE
- Systemic lupus erythematosus
- Tnf
- tumor necrosis factor
- Treg
- Regulatory T cells