Genetic inheritance only explains one facet of disease susceptibility, he adds. “Here the best example is that identical twins have at best 15% to 20% lupus concordance,” he says. “Secondly, even in patients who are on a medical regimen resulting in disease remission, many patients later have serious disease flares, especially lupus nephritis. What causes the flares?”

For a study published in the Annals of Rheumatic Diseases, Dr. Silverman and colleagues conducted an observational study, where taxononomic analyses—including multivariate analysis of beta-diversity—evaluated time-dependent changes in fecal communities from patients with SLE and healthy controls. From gut blooms, the researchers isolated strains and analyzed each of their genomes, and associated surface glycans.

First Longitudinal Study of Its Type

“Our study was the first longitudinal study of its type, with samples obtained over time to more intensively examine whether there were correlated changes in microbiota communities and activity of different disease manifestations,” Dr. Silverman says. “We wondered whether specific changes in the gut microbiome might help explain specific disease manifestations or disease flares.”

Every treatment for lupus involves impairment of host immune defenses, he explains, and if all else fails, doctors use chemotherapy that completely dismantles the immune system. “Yet, if a disease flare results from a shift in intestinal microbiota shift that we can identify, we should be able to develop a means to normalize those shifts,” Dr. Silverman points out. “If this is feasible, we will one day be able to look back at current therapeutic treatments and consider them excessive and potentially dangerous.”

In Almost All Patients With Lupus, Their Gut Communities Are Unstable

The study team assessed measurements of microbiome stability over time and observed that in almost every patient with lupus, their gut communities are unstable and shifting in composition over time (Figure). “This was not previously considered,” Dr. Silverman notes. “Therefore, dysbiosis is almost certain to arise within an unstable community. In a healthy person, there is community resilience, which means that even transient shifts in a community, from stress, intercurrent infection, or changes in diet, will later return to the natural equilibrium in the microcommunities in that individual.”

Dr. Silverman and colleagues suggest encouraging patients to minimize their intake of hyper-processed foods that can be proinflammatory. “Foods with long shelf-lives contain agents that slow down or arrest microbes from spoiling food, but such agents can also affect the health of the beneficial gut microbial community in the intestine, which we need for good health,” Dr. Silverman says. “We should encourage our patients to incorporate foods considered part of the Mediterranean diet, which have no preservatives, and are, therefore, better for our internal communities.”

For future research, the study team would like to see a larger longitudinal multicenter study, with fixed interval sampling every 2 to 3 months over 1 to 3 years. “We also need intervention studies with milder, more targeted antibiotics with microbiome surveillance,” Dr. Silverman adds. “In addition, we would like to see an intervention study with an agent that normalizes gut permeability to see whether this limits inflammation and lowers disease activity. This should include monitoring of the effects of these interventions on antibody responses specific for antigens in gut pathobionts (commensal drivers of autoimmune disease). In theory, such antibody testing could be useful as an objective surrogate biomarker of disease activity.”