Gut Microbes May Predict Lupus Flares

Jennifer Garcia

February 26, 2019

Decreased biodiversity of the gut microbiome (dysbiosis) may be linked to disease activity in patients with lupus nephritis, according to a new study published online February 19 in the Annals of Rheumatic Diseases.

Doua Azzouz, PhD, from the Department of Medicine, New York University School of Medicine, New York City, and colleagues evaluated blood and fecal samples from 61 women with systemic lupus erythematosus (SLE) and compared them with samples from 17 healthy women. Disease activity in the SLE group was assessed with the SLE Disease Activity Index (SLEDAI).

Using rRNA amplification analysis, the researchers found that patients with SLE displayed a fivefold increase in the number of Gram-positive fecal bacteria, specifically Ruminococcus gnavus (RG) (range, 0.00% – 10.79%; mean ± standard deviation [SD], 1.35% ± 2.01%), compared with healthy control persons (range, 0.00% – 1.27%; mean ± SD, 0.25% ± 0.39%; Mann-Whitney, P = .01). RG is a member of the Clostridia class of bacteria.

This outgrowth was noted among all patients in the SLE group; however, it was greatest among those with the highest SLEDAI scores, in whom an eightfold increase in RG abundance was noted (Mann-Whitney, P = .01).

Further, when the researchers stratified patients with SLE according to organ involvement, those with a history of renal disease demonstrated an abundance of RG-specific amplicon sequence variant compared with those who had no renal impairment.

"These findings suggest a novel paradigm in which specific strains of a gut commensal may contribute to the immune pathogenesis of lupus nephritis," the researchers explain.

Patients in the SLE group who had nephritis demonstrated elevations in serum IgG anti-RG2 antibody reactivity. These elevations directly correlated to fecal abundance of RG, a finding that suggests altered gut permeability.

The investigators note that previous studies have documented RG outgrowths in patients with inflammatory bowel disease and ankylosing spondylitis. "[O]ur findings also contribute to evidence of a widening range of inflammatory and autoimmune conditions associated with a 'leaky gut,' " they suggest.

The authors acknowledge that it is unclear whether the RG outgrowths are causative or whether disease activity may have fostered preferential outgrowth.

Azzouz and colleagues emphasize there is a need "to characterise the diversity and genetic features of RG strains and to understand when these strains colonize and expand in patients with lupus."

In doing so, these findings "may lead to development of a biomarker assay that aids both earlier diagnosis and better prognostic determinations," conclude the authors.

The study was supported in part by grants from the National Institutes of Health (NIH), a contract from the National Institute of Allergy and Infectious Disease, an American Recovery and Reinvestment Act supplement, the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH, the Lupus Research Institute, the Judith and Stewart Colton Autoimmunity Center, and the P. Robert Majumder Charitable Trust. New York University has filed intellectual property related to this study. The authors have disclosed no relevant financial relationships.

Ann Rheum Dis. Published online February 19, 2019. Full text

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