Gut bacteria imbalances tied to lupus flares, nephritis

Last Updated: 2019-02-27

By Marilynn Larkin

NEW YORK (Reuters Health) - Gut bacteria imbalances, particularly for the bacterium Ruminococcus gnavus, are linked to systemic lupus erythematosus (SLE) flares and to potentially life-threatening lupus nephritis, researchers say.

"Our report provides previously unsuspected insights into the possible causes of SLE, originating with atypical expansions of certain bacteria residing in our intestines," Dr. Gregg Silverman of NYU Langone Health in New York City told Reuters Health by email. "This isn't really an infection, but more like an imbalance within the otherwise helpful bacteria that we need for general health."

"Although some patients go into remission and don't need to be treated," he said, "many need to take medications to keep their disease under control. With minor exceptions, current treatment involves medications that suppress the immune system."

"If modest interventions are inadequate, we then prescribe more powerful agents, often starting with corticosteroids, then at times resorting to drugs also used for organ transplantation or even chemotherapy that directly kills the immune cells," he said. "Often, such agents are needed to control lupus nephritis, which we found was associated with R. gnavus expansions and strong antibody responses."

"We are optimistic that, if our findings prove correct, we may need only find an intervention that removes a single bacterial toxin - the lipoglycan released by the implicated bacteria - or develop means to have other intestinal bacteria crowd out R. gnavus," he said.

Dr. Silverman and colleagues analyzed matched blood and fecal samples from 61 female patients with SLE and 17 controls. Compared with controls, the microbiome in patients with SLE showed decreased diversity in species richness, with reductions most pronounced in those with a high SLE disease activity index, according to the Annals of Rheumatic Diseases report, online February 19.

Patients with SLE also showed signs of impaired gut barriers ("leaky gut") that may result in immune exposure to gut commensal bacteria, thereby triggering the disease.

Of note, patients with SLE had an overall five-fold greater representation of R. gnavus, as well as corresponding reductions in a bacterial species with putative protective properties. The patients' fecal samples also showed increases in sigA-coated-R. gnavus bacteria.

Further, in three independent cohorts, patients with active lupus nephritis showed elevated serum IgG, mainly to R. gnavus strain-restricted cell wall lipoglycan antigens.

The group's future studies will involve developing better tests for early diagnosis of lupus, as well as better predictors of prognosis. "We will also initiate studies of patients newly diagnosed with lupus to better understand when these bacteria take hold during the disease," Dr. Silverman said.

"We will also take a deep dive into investigating which strains of this otherwise beneficial type of commensal bacteria can become involved in the lupus disease process," he concluded.

Dr. Hariom Yadav, a gut microbiome expert at Wake Forest School of Medicine in Winston-Salem, North Carolina, called the study "fascinating."

"Although the authors have elegantly connected microbiome dysbiosis with increased R. gnavus with SLE and nephritis, it is not known whether microbiome dysbiosis or increased R. gnavus are causative in increasing SLE/nephritis or if these changes are a consequence of the host disease condition," he said in an email to Reuters Health. "Further studies are warranted to address this caveat."

"This study can provide an opportunity for developing bioassays for the R. gnavus cell wall lipoglycan for prognosis of SLE/nephritis," he added. "However, this should be done with robust validation and consistency in clinical cohorts."

SOURCE: http://bit.ly/2XpFs76

Ann Rheum Dis 2019.