Research Is First to Pinpoint a Gut Organism to Lupus, Advancing Understanding of the Microbiome in Autoimmune Disease
NEW YORK, NY. June 9. The Lupus Research Alliance (LRA) announced today that Martin Kriegel, MD, PhD, of the University of Münster is the 2021 Lupus Insight Prize Awardee for his cutting edge research in the understanding of how lupus may be triggered by the gut microbiome — the community of microorganisms such as bacteria, viruses and fungi, that normally live in our guts.
The prestigious Lupus Insight Prize recognizes outstanding researchers who have made a major discovery that promises to advance the understanding of lupus with a high likelihood of improving its diagnosis or treatment. The Lupus Insight Prize was presented to Dr. Kriegel at the FOCIS (Federation of Clinical Immunology Societies) annual meeting by Gary Koretzky, MD, PhD, LRA Scientific Advisory Board Chair and Professor at Weill Cornell Medicine.
In his prior role as Associate Professor at Yale School of Medicine (now at the University of Münster), Dr. Kriegel has found that bacteria that normally live in the gut can ‘leak out’ of the intestine and move into other tissues where they can trigger autoimmune responses.
“Dr. Kriegel’s scientific work uncovering how the microbiome can contribute to lupus and other immune diseases is truly innovative and will provide a direction for further research and new treatments in the years to come,” noted Dr. Koretzky.
Research is First to Pinpoint a Gut Organism Linked to Lupus
Although existing research links alterations in the microbiome to autoimmunity, Dr. Kriegel is the first to identify a particular organism that breaks through the gut lining in lupus. His lab found that in mouse models of lupus, a particular species of bacteria escaped from the gut and entered the liver and lymph nodes where it promoted autoantibody production and overactivation of immune cells called T cells that can cause inflammation. Antibiotics and a vaccine against these bacteria eliminated these autoimmune effects in the mice. Dr. Kriegel then showed that this same species of bacteria is found in the livers of lupus patients.
He also discovered that when another type of bacteria moves from the gut to the liver in mouse models of lupus, it worsens autoimmunity through immune molecules called Toll-like receptor 7 (TLR7) and type I interferon (IFN). These molecules promote inflammation and have long been known to be important in lupus development. Dr. Kriegel found that the same type of bacteria he saw in mice was also found in a subset of lupus patients, and its numbers could be reduced by feeding the mice a resistant starch, a type of fiber that is resistant to digestion in the small intestine.
“Identifying specific species of the microbiome as possible causes of disease pathways in lupus and other autoimmune disorders may help us better understand the development of these conditions. It will also provide a personalized approach to future therapies aimed at the microbiome in humans,” noted Dr. Kriegel.
Although the presence of autoantibodies is prominent in lupus and other autoimmune disorders, what triggers their formation is still not known. Dr. Kriegel’s work has shown that some bacteria living on our skin, in our mouths, and in our guts can cause these autoantibodies to form in people genetically predisposed to autoimmunity. He intends to use the funds from the Lupus Insight Prize to further explore exactly how gut bacteria promote autoimmunity, if they migrate to internal organs, and whether one or more of the bacterial species he identified work through the inflammatory Type I interferon pathway.
“Dr. Kriegel’s work is impacting not only research efforts in lupus but is paving the way for targeted approaches to deplete disease-associated gut microbes in subsets of lupus patients,” said Dr. Teodora Staeva, Chief Scientific Officer of LRA.
Lupus is a chronic, complex autoimmune disease that affects millions of people worldwide. More than 90% of people with lupus are women; lupus most often strikes during the childbearing years of 15-45. African Americans, Latin Americans, Asians and Native Americans are at two to three times greater risk than Caucasians. In lupus, the immune system, which is designed to protect against infection, creates antibodies that can attack any part of the body including the kidneys, brain, heart, lungs, blood, skin, and joints.
About the Lupus Research Alliance
The Lupus Research Alliance is the largest non-governmental, non-profit funder of lupus research worldwide. The organization aims to transform treatment by funding the most innovative lupus research, fostering diverse scientific talent, and driving discovery toward better diagnostics, improved treatments and ultimately a cure for lupus. Because the Lupus Research Alliance’s Board of Directors fund all administrative and fundraising costs, 100% of all donations goes to support lupus research programs.
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