Fecal Microbiota Changes in NZB/W F1 Mice After Induction of Lupus Disease

Background: Gut microbiota is thought to regulate immune homeostasis. The association between gut microbiota and the development of systemic lupus erythematosus remains unclear. This study aims to investigate the differential alteration of gut microbiota after the induction of lupus in a murine model with viral peptide of human cytomegalovirus (HCMV), which is an established murine model of induced lupus. Results: Specifically, we injected HCMVpp65 peptide in peritoneal space in NZB/W F1 mice to induce lupus. Three arms of animal treatment were prepared: intraperitoneal injection of HCMVpp65 peptide, intraperitoneal injection of adjuvant alone, and none injected. Feces of the study animals were collected before and every two weeks after the lupus induction for 16S rRNA sequencing. At 24 weeks of age, pathological investigation of renal tissue from sacrificed mice was conducted. Statistical analysis for dynamics and alteration of the fecal microbiota and lupus-like-activity-related functional prediction of bacterial communities was performed. HCMVpp65 peptide immunization induced lupus-like activities, with a higher level of anti-dsDNA antibodies, creatinine and proteinuria, and severe glomerular damage, compared to the mice treated with none or adjuvant only. A higher Simpson diversity value was measured in mice with injection of HCMVpp65 peptide than those with injection of adjuvant or none, but there have no difference in the species richness estimates, ACE and Chao1. Statistical Analysis of Metagenomic Profiles (STAMP) showed a higher relative abundance of the family (Saccharimonadaceae, Marinifiaceae, and Desulfovibrionaceae) and genera (Candidatus Saccharimonas, Roseburia, Odoribacter, and Desulfovibrio) that were found in HCMVpp65 peptide treated mice, compared to mice injected with adjuvant or none. The predicted metagenomic taxonomic profile showed statistically significant enrichment of flagellar assembly, bacterial motility, and chemotaxis. Conclusion: A significant correlation between increased related genera abundance (Candidatus Saccharimonas, Roseburia, Odoribacter, and Desulfovibrio) and HCMVpp65 peptide immunization induced lupus-like activities was observed. This study confirmed significant changes in gut microbiota after the onset of lupus in a murine animal model.