Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic and often severe multi-organ autoimmune disease characterized by the production of autoantibodies and heterogeneous clinical manifestations. African Americans (AA) and young women are disproportionately affected by SLE, and AAs develop SLE at a younger age with a higher prevalence of kidney involvement (lupus nephritis, LN) compared to other racial/ethnic groups.

Little is known about the etiology of SLE. Genetic inheritance alone is insufficient for developing SLE, suggesting environmental triggers play a role in disease expression. Gut microbiota play a key role in setting the systemic immune tone and influences regulatory and inflammatory immunologic responses. Our study investigates gut microbiome characteristics that may lead to development, progression, and severity of disease in SLE. We hypothesize that gut microbial variation exists at the structural level between patients with SLE (either with or without LN), and healthy controls. Furthermore, we suspect higher microbiome diversity is protective against autoimmunity and a higher proportion of “pro-inflammatory” microbes is a risk factor for SLE and LN.

Methods: We characterized the microbial composition of fecal DNA from samples obtained from AA patients with SLE and from non-SLE AA controls. All participants provided informed consent for research participation and SLE/LN vs control status was confirmed during in-person interview, examination, lab evaluation, and record review. We performed genomic assessment of gut microbial communities using whole genome shotgun sequencing. Gut microbiota was quantified using a sequence-based profiling method. These metagenomes were analyzed against known microbial genome databases (NCBI-NR). Genus abundance profiles were constructed to evaluate microbial species distribution.

Results: 58 samples have been collected (28 SLE/LN and 30 controls) to date. Of these, 44 samples have been sequenced (27 patients and 17 unrelated controls) with the remaining pending at this time. Using metagenomic phylogenetic analysis, 371 species were identified. Principal coordinate analysis between female patients and female controls revealed no significant difference in organism abundance (p-value= 0.5914). In patients with lupus nephritis (n=9) compared to lupus patients without renal disease and controls (n=35), there was no significant difference in abundance at the phylum level (p-value= 0.3681).

Conclusion: Our preliminary studies show that among AA females with SLE and lupus nephritis, gut microbiome composition appears similar to that of unrelated controls. Other similar studies have shown significant differences in microbiome composition between SLE patients and controls, however patients included in our studies had low SLEDAI scores, indicating low disease activity at time of sample collection. We plan to perform multivariate modeling to determine if environmental factors (age, medications, diet, smoking, occupational exposures) in addition to SLE disease status affect microbial composition.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-pathogenic-and-protective-environmental-exposures-on-autoimmune-disease-the-microbiome-effects-on-lupus-mel-study/