Abstract
The association between the gut microbiota and the development of lupus is unclear. We investigated alterations in the gut microbiota after induction of lupus in a murine model using viral peptide of human cytomegalovirus (HCMV). Three treatment arms for the animals were prepared: intraperitoneal injection of HCMVpp65 peptide, adjuvant alone, and PBS injection. Feces were collected before and after lupus induction biweekly for 16S rRNA sequencing. HCMVpp65 peptide immunization induced lupus-like effects, with higher levels of anti-dsDNA antibodies, creatinine, proteinuria, and glomerular damage, compared with mice treated with nothing or adjuvant only. The Simpson diversity value was higher in mice injected with HCMVpp65 peptide, but there was no difference in ACE or Chao1 among the three groups. Statistical analysis of metagenomic profiles showed a higher abundance of various families (Saccharimonadaceae, Marinifiaceae, and Desulfovibrionaceae) and genera (Candidatus Saccharimonas, Roseburia, Odoribacter, and Desulfovibrio) in HCMVpp65 peptide-treated mice. Significant correlations between increased abundances of related genera (Candidatus Saccharimonas, Roseburia, Odoribacter, and Desulfovibrio) and HCMVpp65 peptide immunization-induced lupus-like effects were observed. This study provides insight into the changes in the gut microbiota after lupus onset in a murine model.
Highlights
Systemic lupus erythematosus (SLE) is a prototype of systemic autoimmune diseases characterized by persistent chronic inflammation and production of autoantibodies, anti-dsDNA antibodies
17A were higher in HCMVpp65422-439-immunized mice at 12 weeks post-immunization (24 weeks of age, lupus group) compared with NZB/W F1 mice treated with PBS or adjuvant only
The abundances of the families Akkermansiaceae and Lactobacillaceae were decreased in the three groups at 12 weeks post-immunization, but the difference in Lactobacillaceae abundance was not significant (Supplementary Fig. 3b, c)
Summary
Systemic lupus erythematosus (SLE) is a prototype of systemic autoimmune diseases characterized by persistent chronic inflammation and production of autoantibodies, anti-dsDNA antibodies. It results in dysregulation of cytokines, leading to severe and irreversible tissue injury[1,2]. The reciprocal interplay between the intestinal microbiota and the host immune system maintains tissue h omeostasis[7,8,9]. Autoimmune diseases such as SLE may be associated with changes in the gut microbiota. We investigated the dynamics of the fecal microbiota associated with lupus-like effects in H CMVpp65422-439-immunized mice, compared with mice treated with PBS or adjuvant only
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