| 초록 |
Lupus nephritis (LN), among the worst complications of systemic lupus erythematosus, is driven by immune dysregulation. To identify metagenomic signatures involved in LN pathogenesis, we investigated the fecal pathobionts and validated their function related to host immunity through metabolomic analysis. Stool samples were collected from 37 LN patients and 31 healthy controls (HCs). Total DMA was extracted using the QIAamp DNA Stool Mini Kit and whole metagenomic sequencing was performed on the Illumina NovaSeq platform. Microbial diversity was analyzed by computing alpha and beta diversity using QIME2. Taxonomic profiles, and functional pathway enrichment analysis was conducted using LEfSe and KEGG databases, respectively. SCFA concentrations in fecal samples were quantified using liquid chromatography-mass spectrometry. Baseline characteristics were comparable between groups, except for the older age in the HC group. Alpha diversity, assessed by the Shannon index, did not differ between the two groups, whereas beta diversity showed a significant compositional difference (p=0.005). Taxonomic analysis identified a marked reduction in Eubacterium eligens and Roseburia intestinalis while an increased proportion of Rumonicoccus gnavus, Veillonella atypica, V. parvula, and V. dispar in LN patients (FDR < 0.05). Metagenomic pathway analysis revealed 24 altered pathways, including nine linked to carbohydrate metabolism. Gene family analysis further demonstrated a reduction in hydroxyacyl-CoA dehydrogenase (HADH), a key enzyme in butyric acid synthesis, with E. eligens as its primary contributor. The fecal SCFA analysis showed significantly reduced butyrate level in LN patients (p=0.027), suggesting a disruption in butyrate-mediated anti-inflammatory effect that aligned with the observed depletion of E. eligens and HADH gene abundance. We found a notable reduction in E. eligens, accompanied by decreased fecal butyrate production in LN patients. These findings highlight a potential link between microbial alterations, impaired SCFA metabolism, and the immune dysregulation observed in LN. |