Gregg Silverman, MD

New York University, NY

2013 Environmental Triggers, Human Lupus Biology

The Microbiome and SLE

Gregg Silverman, MDThe Study and What It Means to Patients

"We are applying the most cutting edge technologies to search for evidence that germs in our bodies serve as triggers for lupus. Our studies may lead to new approaches for early diagnosis and therapeutic intervention."

Summary

The human gut is inhabited by hundreds of different species of microorganisms, many of which help us by breaking-down food and protecting us from infection. But certain resident germs have recently been implicated as triggers for specific chronic diseases. We are using cutting-edge DNA sequencing technology to identify all the gut germs in over 100 lupus patients. This survey of the gut "microbiome," the first in lupus patients, might reveal new strains of bacteria that are risk factors for lupus. This knowledge could be used to predict who will get the disease, allowing for early treatment or prevention.

Scientific abstract

SLE is a complex autoimmune disease with great clinical heterogeneity. Despite significant progress in genetic surveys, the cumulative evidence supports observations first made in twin studies that much of the risk for disease derives from environmental factors. Of all potential factors, the influence of our microbiome (i.e., the consortium of microorganisms that reside within our bodies) has recently been implicated in other inflammatory and autoimmune clinical diseases. Moreover, certain species in the gut microbiome can influence responses from both innate and adaptive immunity. While certain bacterial species can modulate T cell responses, others produce factors that induce interferon production, which we speculate may be linked to lupus pathogenesis. Unbiased surveys for the representation of bacterial species can now be readily performed using high throughput DNA sequencing of 16S rRNA genes. We speculate that the specific microbiome of a SLE patient directly influences the initiation and perpetuation of clinical active lupus, which may involve the induction of the disease-associated interferon signature in peripheral blood cells. Our project will perform the first surveys of the gut associated microbiota of SLE patients, and assess for the possible relationships between SLE disease activity, clinical manifestations and effects on the host immune system.