Background/Purpose: From a cross-sectional cohort, we have recently identified a candidate human gut pathobiont, Ruminococcus gnavus (RG) of the Lachnospiraceae family and Blautia genus that was linked to active Lupus nephritis (LN)(1). LN patients often displayed gut blooms of RG, concordant with serum IgG anti-RG antibody responses that appeared intertwined with anti-dsDNA responses implicated in renal pathogenesis. The dynamics of RG representation within SLE microbiota ecosystems have not been investigated. The genomic sequences of few RG strains have been reported, and these vary greatly in genome structure, gene representation and sequence.

Methods: A total of 53 fecal samples from 16 SLE patients and 63 samples from 11 CTL, at 2-12 time-points were studied, and patients were characterized for demographics, and clinical disease activity. High-throughput 16S rRNA amplicon libraries from fecal samples were analyzed using QIIME 2 and DADA2 (1). Hundreds of individual fecal RG colonies from two active LN patients were isolated and subjected to whole genome sequencing (WGS), with phylogenetic assignments in part based on inter-strain average nucleotide identity, multi-locus sequence typing and reference-guided genomic assemblies.

Results: Our analysis confirmed highly conserved patterns of gut community representation in SLE patients that displayed reduced microbiota richness, which was most pronounced in patients with high SLEDAI (p= 0.0023) and LN (p=0.002), confirming earlier reported findings [1]. Beta diversity analysis showed significant heterogeneity in SLE microbiome compared to CTL (p= 0.001). Similarly, RG abundance was greater in patients with high SLEDAI (p= 0.0021) and LN compared to CTL (p= 0.003). Tracking of the dynamic representation of RG at different time points within individual subjects, in CTL and many Lupus patients showed little or no detectable perturbations. Strikingly, in LN patients examined, there was a direct correlation between representation of RG and the SLEDAI score of overall disease activity in 53% of LN patients overtime. WGS analysis of the RG isolated colonies discovered four distinct RG strains with large genomic variations, which differ from previously reported RG  strains from other diseases and healthy donors.

Conclusion: Our findings suggest that intestinal blooms of the RG candidate pathobiont correlate with serious increases in Lupus disease activity, and especially LN. In pilot studies we have isolated and characterized the genomes of the first RG strains from active SLE patients. Our findings suggest that both dynamic representation and colonization by specific RG strains identified by their genomic composition, may have implications for the host-pathobiont relationship and the immune activation that is integral to Lupus pathogenesis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dynamic-changes-in-microbiota-representation-of-a-gut-pathobiont-and-clinical-disease-activity-in-patients-with-lupus-nephritis/