Blooms of specific gut bacteria may trigger lupus flares, study suggests

Researchers found lupus patients had more instability in gut microbiomes

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Blooms in the growth of a specific species of gut bacteria, called Ruminococcus blautia gnavus or RG, may trigger disease flares in people with lupus, a new study suggests.

“Our findings provide the strongest evidence to date that silent growths of Ruminococcus blautia gnavus are tied to active serious renal [kidney] disease in lupus patients,” Doua Azzouz, PhD, the study’s first author at NYU Grossman School of Medicine, said in a press release.

The study, “Longitudinal gut microbiome analyses and blooms of pathogenic strains during lupus disease flares,” was published in the journal Annals of the Rheumatic Diseases

Lupus is characterized by flares or relapses, where symptoms suddenly worsen. The causes of these disease flares are poorly understood.

Here, researchers investigated whether changes in the gut microbiome — the community of bacteria and other microorganisms that make their home in the human digestive tract — were associated with lupus flares.

The study included 16 women with lupus who were monitored for flare activity over the course of several months to years. During follow-up, a total of 44 stool samples were collected from the patients, and the researchers used genetic analyses to assess the species of bacteria within the samples. For comparison, they also analyzed stool samples from 22 female volunteers without lupus, who were similar to the patients in demographic background.

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Lupus patients experience ‘blooms’ of bacteria

Results showed lupus patients tended to have more instability in their gut microbiomes than people without the disease. Lupus patients commonly experienced “blooms,” where a specific type of bacteria would suddenly grow to substantial numbers.

In analyzing these changing dynamics and their relationship with disease activity, researchers noticed that blooms of the RG bacteria were seen during disease flares in four of the nine patients who had lupus nephritis, a severe complication of lupus characterized by kidney damage and inflammation. One patient who did not have lupus nephritis also experienced a bloom of RG during a disease flare of multiple joint inflammation.

By comparison, RG abundance showed “remarkable stability” over time for people without lupus, the researchers wrote, adding that these data suggest “that RG blooms can contribute to the clinical pattern of relapsing-remitting disease activity that occurs in many lupus patients despite close clinical monitoring and treatment.”

Researchers isolated RG bacteria from some of the samples collected during flares for further analysis. Genetic tests showed that these bacteria expressed many genes that have been previously found in bacteria from people with inflammatory bowel disease (IBD), another chronic autoimmune disease. The team speculated these genes might make the bacteria better suited to thrive in an environment with more inflammation, which occurs in both lupus and IBD.

Bacteria could trigger activity in immune system

Though these findings suggest RG blooms occur at similar times as lupus flares, particularly those associated with kidney disease, researchers noted these bacteria live only in the intestines, so they aren’t directly causing disease worsening. Instead, the team postulated the growth of RG bacteria might trigger activity of the patient’s immune system, which in turn leads to lupus worsening. In line with this idea, researchers identified antibodies that could react to components of the RG bacteria in some lupus patients.

The team stressed further research will be needed to validate this small study and expand on the mechanisms. They also noted some flares occurred in the absence of a RG bloom, so while these bacteria may be responsible for some flares, they definitely aren’t the only cause. Still, the team says these findings support the idea that better understanding the connection between gut bacteria and disease flares could open new avenues to treat lupus.

“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,” said Gregg Silverman, MD, professor at Grossman School and co-author of the study. “Such future treatments for lupus, especially lupus nephritis, could potentially decrease the use of drugs designed to dampen the immune system and instead promote the use of less-toxic antibacterial agents, probiotics or dietary regimens that prevent imbalances such as Ruminococcal blooms in the local gut bacterial population.”