Intestinal Tract Bacteria may Heighten Lupus Symptoms

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Growth of bacteria in the intestinal tract is associated with increased lupus activity, particularly lupus nephritis, according to recent research.

In a study published in theAnnals of Rheumatic Diseases, researchers analyzed fecal microbiota from patients with systemic lupus erythematosus (SLE) for possible disease-causing species and evaluated their relationship with the patient’s immunity.

The study is the first to offer evidence of an association between lupus and intestinal growths of Ruminococcus gnavus, an anaerobic Gram-positive taxon. In the human gut, RG has been found to break down complex polysaccharides, including those in the intestinal mucus layer, possibly leading to a leaky gut.

Investigators, in a cross-sectional study, analyzed fecal samples from 61 female patients with lupus and compared them to 17 women without lupus. They used the SLE disease activity index (SLEDAI) to categorize patients’ disease states.

According to study data, SLE patients had an average 5-fold overabundance of RG (range 0.00%-10.79%, mean +/-SD 1.35% +/-2.01%) compared to controls (0.00%-1.27%, 0.25%+/-0.39%). The most significant growth appeared in patients with high disease activity, particularly lupus nephritis (LN).

Researchers also identified higher levels of gut secretory Immunoglobulin A in patients with lupus-a factor associated with gut barrier dysfunction. In particular, they unearthed a direct relationship with lupus disease activity and with LN and the highest levels of serum Immunoglobulin G anti-RG antibody responses. Based on these findings, they hypothesized RG contributes to the onset and/or flares of lupus disease, especially LN.

These results point to significant contributions to the field of knowledge surrounding LN, the investigators said. Not only were patients with lupus found to have characteristic gut microbiome microbial imbalance patterns that directly paralleled disease activity, but SLE patients also commonly presented signs of impaired gut barriers that could result in immune exposure to gut commensal bacteria.

Ultimately, researchers said, their findings open the door to other areas of study. Additional research is needed into how outgrowths can affect the overall pathogenesis of lupus and the LN’s immune complex-mediated pathogenesis. Results could also play a role in developing bioassays that can potentially predict LN risk, they wote.

REFERENCE:

Azzouz D, Omarbekova A, Heguy A, Schwudke D, Gish N, Robin B, Caricchio R, Buyon J, Alekseyenko A, Silverman G, Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal. Annals of Rheumatic Diseases (2019), doi: 10.1136/annrheumdis-2018-214856.