Lupus gut microbiota transplants cause autoimmunity and inflammation
Autor: | Yiduo Sun, Yiyangzi Ma, Feng Gao, Ruru Guo, Lun He, Haitao Niu, Xin Li, Liangjing Lu, Gregg J. Silverman, Guobing Chen, Qiang Wei, Zhao Li, Mengtao Li, Jiali Yuan |
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Rok vydání: | 2021 |
Předmět: |
Immunology
Autoimmunity Inflammation Gut flora medicine.disease_cause Pathogenesis Mice Immune system immune system diseases Animals Germ-Free Life Humans Lupus Erythematosus Systemic Immunology and Allergy Medicine Histidine skin and connective tissue diseases Systemic lupus erythematosus biology business.industry Fecal Microbiota Transplantation biology.organism_classification medicine.disease Phenotype Gastrointestinal Microbiome Mice Inbred C57BL biology.protein Female medicine.symptom Antibody business |
Zdroj: | Clinical Immunology. 233:108892 |
ISSN: | 1521-6616 |
Popis: | 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 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. |
Databáze: | OpenAIRE |
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