Targeting a Bacterial Toxin To Help Treat Lupus Nephritis

Lupus nephritis, a serious inflammation of the kidneys, affects half of SLE patients.

In previous studies, lupus nephritis flares have been linked to the bacteria Ruminococcus gnavus and a toxin it produces.

This bacteria is also found in the guts of people without lupus, where it is found at low levels and doesn’t cause an immune response. A recent study finds that targeting the bacteria or an immune cell receptor it activates may help treat lupus nephritis. Half of the lupus nephritis patients in this study had increased growth of this bacterium and these patients also had signs of increased inflammation and antibodies against the bacterium’s toxin.

In preclinical models, the researchers found that exposure of this bacteria to the guts of mice with lupus triggered inflammation and renal damage.

Blocking the receptor on the immune cells reduced the amount of inflammation.

“Our findings also set the stage for using selective antibiotic drugs to block these bacterial growths, or other inhibiting drugs to block the toll-like receptor 2 toxins produced by these bacterial blooms, to treat lupus nephritis,” said Gregg Silverman, a professor at NYU Grossman School of Medicine and lead author on the study.

This work adds to the large body of work that shows a connection between autoimmune diseases and the gut microbiome.

Citations

Azzouz, D., Omarbekova, A., Heguy, A., Schwudke, D., Gisch, N., Rovin, B. H., Caricchio, R., Buyon, J. P., Alekseyenko, A. V., & Silverman, G. J. (2019). Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal. Annals of the rheumatic diseases, 78(7), 947–956. https://doi.org/10.1136/annrheumdis-2018-214856

Amarnani, A., Rivera, C. F., Cornwell, M., Weinstein, T., Azad, Z., Gottesman, S. R. S., Loomis, C., Lee, A., Ullah, N., Prasad, J., Yi, M., Cooney, L., Barnes, B. J., Gisch, N., Ruggles, K. V., Ramkhelawon, B., & Silverman, G. J. (2027). A pathogenic gut lipoglycan drives systemic thromboinflammation in lupus nephritis. Annals of the rheumatic diseases, S0003-4967(26)00146-9. Advance online publication. https://doi.org/10.1016/j.ard.2026.03.002