Proinflammatory and autoimmunogenic gut microbiome in systemic lupus erythematosus

Chen, B.; Jia, X.-m.; Xu, J.-y.; Zhao, L.-d.; Ji, J.-y.; Wu, B.-x.; Fei, Y.-y.; Yang, H.-x.; Chen, H.; Zuo, X.-x.; Li, H.; Pan, W.-y.; Wang, X.-h.; Ye, S.; Guo, D.-g.; Wang, L.; Li, J.; Peng, L.-y.; Zheng, W.-j.; Zhang, W.; Zhang, F.-c.; Zhang, J.-m.; He, W.; Cao, X.-t.; Liu, D.-p.; Wang, J.; Zhang, X.

doi:10.1101/621995

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bioRxiv · 10.1101/621995

Proinflammatory and autoimmunogenic gut microbiome in systemic lupus erythematosus

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Abstract

Systemic lupus erythematosus (SLE), characterized by chronic inflammation and multi-organ damage, has been suggested to associate with gut dysbiosis, but knowledge is limited from small sample size and 16s rRNA-based studies. To shed new light on the role of microbiota in SLE development, we analyzed the fecal metagenome of 117 treatment-naive SLE patients and 115 sex- and age-matched healthy controls (HC) by deep-sequencing; in addition, 52 of the aforementioned patients have post-treatment fecal metagenome for comparison. We found significant differences in microbial composition and function between SLE and HC, revealing multiple plausible contributing bacterial species and metabolic pathways in SLE. In-depth SNP-based analysis revealed an oral-microbiome origin for two marker species, strengthening the importance of bacterial translocation in disease development. Lastly, we confirmed experimentally that peptides of SLE-enriched species mimicking autoantigens such as Sm and Fas could trigger autoimmune responses, suggesting a potential causal role of gut microbiota in SLE.

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Chen, B., Jia, X.-m., Xu, J.-y., Zhao, L.-d., Ji, J.-y., Wu, B.-x., Fei, Y.-y., Yang, H.-x., Chen, H., Zuo, X.-x., Li, H., Pan, W.-y., Wang, X.-h., Ye, S., Guo, D.-g., Wang, L., Li, J., Peng, L.-y., Zheng, W.-j., Zhang, W., Zhang, F.-c., Zhang, J.-m., He, W., Cao, X.-t., Liu, D.-p., Wang, J., Zhang, X.. 2019-04-29. Proinflammatory and autoimmunogenic gut microbiome in systemic lupus erythematosus. https://doi.org/10.1101/621995

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