Lupus gut microbiota transplants cause autoimmunity and inflammation

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 16 s 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 (GF) 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 GF mice caused GF mice to develop a series of lupus-like phenotypic features, including increased serum autoimmune antibodies, imbalanced cytokines, altered distribution of immune cells in mucosal and pe-ripheral 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 patho-genesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms inter-twined with autoimmune activation in SLE.

Automated summary

The study found different microbial species in SLE patients compared to healthy controls, and fecal transfer from SLE patients to GF mice induced lupus-like phenotypic features in the mice. The interplay of gut microbial and histidine metabolism may be a mechanism intertwined with autoimmune activation in SLE.