A new study provides the ‘strongest evidence to date’ that certain species of bacteria can make the body’s immune system attack its own tissues

Systemic lupus erythematosus, an autoimmune disease characterized by widespread inflammation and potential tissue damage in various organs, often leads to lupus nephritis in approximately half of patients. Among them, a quarter may progress to end-stage renal disease, necessitating regular blood dialysis or kidney transplantation.

Recent research conducted by NYU Grossman School of Medicine reveals a correlation between recurrent episodes of systemic lupus erythematosus, where the body’s immune system attacks its own tissues, and an increase in the abundance of a particular gut bacterium called Ruminococcus blautia gnavus.

The study, which spanned four years and included 16 women of diverse racial backgrounds with lupus, found that five of the participants experienced disease flare-ups concurrently with substantial growth of R. blautia gnavus in their gut. Systemic lupus erythematosus is characterized by inflammatory damage, particularly in the kidneys, as well as joints, skin, and blood vessels. Four of the patients with R. gnavus blooms had severe cases of lupus nephritis, the most common form of the disease affecting the kidneys, while one had a severe form involving joint inflammation.

The team’s findings, published in the Annals of Rheumatic Diseases today, identified 34 genes associated with the growth of R. blautia gnavus in individuals with inflammation. While the precise causes of lupus, which affects up to 1.5 million Americans, remain unknown, many experts speculate that bacterial imbalances trigger inherited genetic factors responsible for the development of the disease.

Additionally, the study explored the binding strength of immune system antibodies in these patients to structures within the bacterial wall, resembling their response to invading viruses. The antibodies exhibited a notable affinity for particular bacterial lipoglycan molecules, known to trigger inflammation. These lipoglycans were found to be prevalent in R. gnavus strains present in lupus patients but not in healthy individuals. Since antibodies contribute significantly to the damage inflicted on the body in this disease, the researchers emphasize that this diagnostic antibody response underscores the significant role played by R. gnavus in the development of the autoimmune disorder.

“Our findings provide the strongest evidence to date that silent growths of Ruminococcus blautia gnavus are tied to active serious renal disease in lupus patients,” remarked study lead investigator Doua Azzouz, PhD.

“Interestingly, our study also established this common bacterial link among a racially diverse group of females with varying forms of lupus,” added Azzouz.

Lupus is more prevalent among women than men, and it disproportionately affects individuals of Black, Hispanic, and Asian descent compared to those of White ethnicity.

“Our goal is to use our growing understanding of the biological pathways that underpin the disease to develop new treatments that prevent or treat flares for all forms of lupus,” commented study senior investigator and immunologist Gregg Silverman, MD.

Professor Silverman, the Mamdouha S. Bobst Professor of Internal Medicine in the Departments of Medicine and Pathology at NYU Langone Health, expressed that future treatments for lupus, particularly lupus nephritis, could potentially reduce reliance on immune-suppressing medications. Instead, he suggested the promotion of less-toxic approaches such as antibacterial agents, probiotics, or dietary interventions that prevent imbalances like Ruminococcal blooms in the gut bacterial population or microbiome.

Previous research conducted by Professor Silverman’s team demonstrated that R. gnavus blooms contribute to the weakening of the gut wall barrier, leading to bacterial leakage, which subsequently triggers inflammatory responses and an overactive immune system.

In addition to their current findings, Professor Silverman, who also serves as the associate director of rheumatology at NYU Langone, plans to expand the research by including a larger number of patients from different medical centers. The team intends to conduct further experiments using mouse models of lupus to investigate how R. gnavus colonization initiates lupus and whether the presence of R. gnavus accelerates or impacts the severity of flares and inflammation in mice bred to develop lupus-like symptoms.

The researchers also aim to explore various lipoglycan molecules derived from different strains of R. gnavus. Their objective is to identify if specific parts of the molecular structure play a critical role in triggering inflammation or if other lipoglycans elicit immune responses associated with lupus or other gut-related diseases, such as Crohn’s disease.

For this study, the researchers utilized stool and blood samples from lupus patients undergoing treatment at NYU Langone. All study participants were closely monitored for disease flare-ups. The test results were compared with those of 22 female volunteers of similar age and racial background who did not have lupus and were in overall good health.

Source: 10.1136/ard-2023-223929

Image Credit: Shutterstock