A recent study by NYU Grossman School of Medicine revealed a correlation between bacterial blooms of the gut bacterium Ruminococcus blautia gnavus and flare-ups of disease in women with Lupus Nephritis, which is one of the most prevalent and severe disease manifestations occurring in more than 40% of Lupus patients. A quarter of those individuals may experience end-stage renal disease, potentially needing regular blood dialysis or kidney transplantation.
The research, which spanned over four years and included 16 women from diverse racial backgrounds, found that five women experienced bacterial blooms of R. blautia gnavus at the same time as lupus flare-ups.
Lupus is a systemic autoimmune disease characterized by damaging inflammation that affects various organs such as the kidneys, joints, skin, and blood vessels that affects approximately 1.5 million Americans and over 5 million globally. Lupus is more common in women than men and African-American women are three times more likely to get Lupus than Caucasian women. Lupus is also more common in Hispanic, Asian, and Native American women.
The study used stool and blood samples from lupus patients receiving treatment at NYU Langone, with all participants closely monitored for disease flare-ups. Results were compared with 22 healthy female volunteers of similar age and racial background who did not have lupus.
The findings, published in the Annals of Rheumatic Diseases, identified 34 genes associated with the bacterium’s growth in individuals with inflammation. Although the specific causes of lupus remain unknown, one hypothesis is that bacterial imbalances trigger inherited genetic factors responsible for the disease.
The study also explored the binding of immune system antibodies to structures in the bacterial wall. These antibodies exhibited a strong affinity for specific bacterial lipoglycan molecules known to trigger inflammation. These lipoglycans were found to be prevalent in R. blautia gnavus strains in lupus patients but not in healthy individuals. Antibodies play a significant role in the body damage associated with lupus, and the researchers suggest that this diagnostic antibody response highlights the crucial role played by R. blautia gnavus in the autoimmune disease.
Using an antibody biomarker test to detect the newly identified R. blautia gnavus strain-related lipoglycan could potentially assist in the early diagnosis of Lupus Nephritis, leading to improved decision-making in therapy and targeted treatment of pathobiont strains.
The researchers believe that understanding the disease’s biological pathways is key to developing new treatments that prevent or treat lupus flares. Specifically, treatments for lupus nephritis could potentially reduce the use of immune-dampening drugs in favor of less-toxic antibacterial agents, probiotics, or dietary regimens that prevent imbalances like Ruminococcal blooms in the gut microbiome. Previous research by Silverman’s team demonstrated that R. blautia gnavus blooms weaken the gut wall barrier, leading to bacterial leakages that trigger inflammatory and overactive immune responses.
The small sample is a limitation of the single-centre observational pilot study. However, the researchers plan to extend their research to involve more patients from other medical centers and conduct further experiments using mouse models of lupus. These experiments will investigate how R. blautia gnavus colonization triggers lupus and whether it accelerates or affects the severity of flares and inflammation in lupus-like mouse models. Additionally, the team intends to experiment with different lipoglycan molecules from various R. blautia gnavus strains to determine if specific structural components are key triggers of inflammation or if other lipoglycans prompt immune responses associated with lupus or other gut diseases like Crohn’s.
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