Lupus flare-ups linked to bacterial growth in gut

Bacterial blooms of the gut bacterium Ruminococcus blautia gnavus have been found to coincide with recurrent bouts of systemic lupus erythematosus (SLE), according to new research conducted by New York University (NYU) Grossman School of Medicine, US. The study, which looked at stool and blood samples of 16 women of diverse racial backgrounds with lupus, revealed that five of them experienced disease flare-ups at the same time as significant growth in the R. blautia gnavus population in their gut over a four-year period.

Systemic lupus erythematosus is an autoimmune disease characterised by the immune system attacking its own tissues, leading to damaging inflammation, particularly in the kidneys, joints, skin, and blood vessels. In this study, four patients who had R. blautia gnavus blooms also had severe cases of lupus nephritis, the most common kidney-specific form of the disease. Additionally, one patient had a severe form of lupus involving inflammation in multiple joints.

The research, published in the Annals of Rheumatic Diseases, involved analysing the gut bacterial blooms in these lupus patients and identifying 34 genes that were already known to be linked to the growth of R. blautia gnavus in individuals with inflammation. Although the specific causes of lupus are still unknown, experts believe that bacterial imbalances may trigger inherited genetic factors that contribute to the disease.

The study also examined how the patients’ immune system antibodies bonded to structures in the bacterial wall, similar to their response to invading viruses. The antibodies exhibited a strong affinity for specific bacterial lipoglycan molecules, which are known triggers of inflammation. These lipoglycans were found to be common in R. blautia gnavus strains in lupus patients but not in healthy individuals. The researchers emphasised that antibodies play a major role in damaging the body in lupus, and the diagnostic antibody response observed in this study highlights the significant role played by R. blautia gnavus in the development of this autoimmune disease.

Lead investigator Dr Doua Azzouz, stated, “Our findings provide the strongest evidence to date that silent growths of R. blautia gnavus are tied to active serious renal disease in lupus patients.” The study also established a common bacterial link among a racially diverse group of females with various forms of lupus. It is worth noting that lupus is more prevalent in women than in men and affects more individuals of Black, Hispanic, and Asian ethnicities than those of White ethnicity.

The researchers aim to leverage their growing understanding of the biological pathways underlying lupus to develop new treatments that prevent or treat disease flare-ups in all forms of the condition. The goal is to reduce the reliance on drugs that suppress the immune system, and instead explore the use of less-toxic antibacterial agents, probiotics, or dietary regimens that prevent imbalances in the gut bacterial population, such as Ruminococcal blooms.

Previous research by the team demonstrated that R. blautia gnavus blooms weaken the gut wall barrier, leading to bacterial leakage and triggering inflammatory and overactive immune responses. The researchers plan to expand their current research to include more patients from other medical centres. They also intend to conduct further experiments using mouse models of lupus to investigate how R. blautia gnavus colonisation triggers lupus and whether it accelerates or affects the severity of flares and inflammation in mice bred to develop lupus-like symptoms.

The team also plans to conduct experiments on various lipoglycan molecules from different strains of R. blautia gnavus to determine if any specific part of the molecular structure is responsible for triggering inflammation or if other lipoglycans also elicit an immune response associated with lupus or other gut.