Lupus flare-ups strongly linked to specific bacterial growth in the gut

New research from NYU Grossman School of Medicine shows bacterial overgrowths of the gut bacteria Ruminococcus blautia gnavus occurred alongside disease flares in five of 16 women with lupus of various racial backgrounds studied over a period of time. of four years. Systemic lupus erythematosus involves damaging inflammation, particularly in the kidneys, but also in the joints, skin, and blood vessels. Four of these study patients with R. gnavus outbreaks had severe cases of the most common and kidney-specific form of the disease, lupus nephritis, while another had a severe example of lupus involving a inflammation of several joints.

Publish in the Annals of rheumatic diseases Online on June 27, the team’s analysis of the gut bacterial overgrowths of these lupus patients identified 34 genes that had previously been linked to the growth of the bacteria in people with inflammation. While the specific causes of lupus, which affects up to 1.5 million Americans, remain unknown, many experts suspect that bacterial imbalances trigger inherited genetic factors responsible for the disease.

This study also investigated how well these patients’ immune system antibodies bound to bacterial wall structures, much like they would an invading virus. These antibodies showed strong affinity with specific bacterial lipoglycan molecules which are known triggers of inflammation. These lipoglycans have been found to be common in strains of R. gnavus in lupus patients, but not in healthy people. Antibodies are a major cause of body damage in this disease, and this diagnostic antibody response, the researchers say, highlights the important role played by R. gnavus in autoimmune disease.

“Our results provide the strongest evidence to date that silent growths of Ruminococcus blautia gnavus are linked to severe active kidney disease in patients with lupus,” said Doua Azzouz, PhD, principal investigator of the study.

“Interestingly, our study also established this common bacterial link among a racially diverse group of women with different forms of lupus,” said Azzouz, postdoctoral researcher in the Department of Medicine at NYU Langone Health. Lupus is more common in women than in men, and the disease affects more blacks, Hispanics and Asians than whites.

“Our goal is to use our growing understanding of the biological pathways that underlie the disease to develop new treatments that prevent or treat flare-ups of all forms of lupus,” said Gregg Silverman, MD, principal investigator and immunologist at the study.

“These future treatments for lupus, particularly lupus nephritis, could potentially reduce the use of drugs designed to suppress the immune system and instead promote the use of less toxic antibacterial agents, probiotics, or diets that prevent imbalances such as ruminococcal overgrowths in the local gut bacterial population, or microbiome,” said Silverman, Mamdouha S. Bobst Professor of Internal Medicine in the Departments of Medicine and Pathology at NYU Langone Health.

Previous research by Silverman’s team has shown that R. gnavus overgrowths weaken the gut wall barrier, causing bacterial leakage which in turn triggers inflammatory and overactive immune responses.

Silverman, who is also associate director of rheumatology at NYU Langone, says the team plans to expand the current research to more patients at other medical centers. The team is also planning further experiments in mouse models of lupus to see how colonization of R. gnavus triggers lupus and whether in mice bred to develop lupus-like symptoms, R. gnavus blooms accelerate or affect otherwise the severity of flare-ups and inflammation.

The researchers say they also want to experiment with various lipoglycan molecules from different strains of R. gnavus to see if a particular part of the molecular structure is key to triggering inflammation or if other lipoglycans also elicit a response. immunity related to lupus or other bowel diseases, including Crohn’s disease.

For the study, researchers used stool and blood samples from lupus patients treated at NYU Langone. All study participants were closely monitored for disease flares. The test results were compared with those of 22 female volunteers of similar age and racial background who did not have lupus and were otherwise healthy.

As an autoimmune disease, systemic lupus erythematosus can lead to widespread inflammation and long-term tissue damage in affected organs. According to the researchers, about half of patients develop lupus nephritis, of which a quarter are likely to suffer from end-stage renal disease that may require regular blood dialysis and even kidney transplantation.

Financial support for the study was provided by National Institute of Health grants UL1TR000038, P30CA016087, R01AR42455, P50AR070591, and HHSN272201400019C. Additional financial support was provided by the Lupus Research Alliance, the Judith and Stewart Colton Autoimmunity Center at NYU Langone, and the P. Robert Majumder Charitable Trust.

Besides Silverman, other NYU Langone researchers involved in this study are Ze Chen, Peter Izmirly, Lea Ann Chen, Zhi Li, Chongda Zhang, Adriana Heguy, Davis Mieles, Kate Trujillo, Alejandro Pironti, Gregory Putzel, David Fenyo, and Jill Buyon . Other study co-investigators are Dominik Schwudke and Nicolas Gisch, of the Leibniz Lung Center in Borstel, Germany; and Alexander Alekseyenko of the Medical University of South Carolina in Charleston.