Flares of systemic lupus erythematosus (SLE), particularly those involving severe kidney disease, were associated with growth spikes of the gut bacteria Ruminococcus blautia gnavus in a small, 4-year observational study that also demonstrated an underlying, inherent instability in the gut microbiome of patients with SLE.
Of 16 patients with SLE studied during the provision of routine care and monitoring, 5 had R. gnavus blooms that were “strikingly concordant with periods of raised disease activity,” Gregg J. Silverman, MD, of NYU Grossman School of Medicine, New York, and coinvestigators reported in Annals of the Rheumatic Diseases.
Dr. Gregg Silverman
Four of the five patients with flare-associated R. gnavus blooms had lupus nephritis (LN); the other had a flare involving inflammation in multiple joints. The four patients with concurrent LN and spikes in R. gnavus also represented almost half of patients who had LN disease flares (four of nine) during the study period. The nine patients in the study with renal involvement, and the four with concurrent R. gnavus spikes and flares, represented different races and ethnicities.
The findings build upon research published by the NYU group several years ago showing that patients with SLE had more R. gnavus in the gut than similar patients without the disease, and that flares closely tracked major increases in R. gnavus growth. Evidence of R. gnavus expansions in patients with SLE now comes from several cohorts in the United States as well as cohorts in Europe and China, the researchers noted in their new paper.
An underlying, unstable microbiome
The new study at NYU took a “deeper dive” than previous research, looking at individuals over a longer period of time, Dr. Silverman, the study’s senior investigator and associate director of rheumatology at NYU Langone Health, said in an interview. Blood and a total of 44 stool samples from the 16 patients were analyzed, as were a total of 72 stool samples from 22 healthy control volunteers.
Importantly, he said, the gut microbiome in patients with SLE was found to be inherently unstable over time, compared with the microbiota communities of the controls. “There was an instability, a shifting dynamic composition of the microbiome [in patients with lupus]. ... Healthy individuals had more of a balance, with small changes over time” and a stable, low abundance of R. gnavus, Dr. Silverman said.
Transient expansions of several pathogenic species occurred in some of the patients with lupus (and not in controls), but blooms of R. gnavus were the most common. The researchers said in their paper that they “speculate that susceptibility for specific clinical features during R. gnavus blooms reflect in part differences in genetic susceptibility of the patient.”
Patients on cytotoxic agents or antibiotics were excluded from the study, but the study was not designed to disentangle the potential influence of diet or prior antibiotic exposure, they noted. Larger studies are needed that are better controlled and that include more frequent assessments, Dr. Silverman added.