Candidate Pathobiont in Lupus: Genomic Variation and Pathogenesis
The microbiome is the community of bacteria, viruses, and fungi that reside in everyone’s body, in the gut and on our skin. A robust microbiome is essential for good health, and changes in the species that make up the microbiome have been linked to many different disease states. Dr. Silverman has found one particular species of bacteria that is present at high levels in the intestines of lupus patients with kidney disease. With his Lupus Mechanisms and Targets Award from the LRA, he will test if this strain of bacteria has a role in causing lupus.
What this means for people with lupus
Dr. Silverman has found a species of bacteria that is more prevalent in the gut of people with lupus than among healthy people who served as the control group. In his future work he hopes to see if detection of this species of bacteria might help in the earlier diagnosis of those at risk of developing kidney disease.
From surveys of the gut microbiome of Lupus patients, we have identified a candidate human pathobiont, Ruminococcus gnavus (RG) of the family Lachnospiraceae that is linked to active Lupus nephritis. Species are assigned based on genome sequence and growth characteristics, and by comparisons of genome sequence and phylogenic trees, and a pathogenic strain may differ by a single gene. Given that few RG strains have been characterized at the genome level, and none previously from Lupus patients, we propose Proof-of-Concept studies of disease-associated bacteria that will investigate how variations in genes and genome composition in RG strains from Lupus patients may affect autoimmune pathogenesis. These studies will use both in vitro and in vivo systems in which we compare the consequences of colonization of transgenic mice by individual RG strains from healthy subjects and active Lupus nephritis patients and other subjects. We will thereby dissect the mechanisms triggered by different strains of this candidate pathobiont. Identification of the RG strains, and RG genes and gene variation(s), with pathogenic properties could lead to earlier diagnosis of at-risk individuals and more effective novel therapeutic interventions.