Microbiome Research in Systemic Autoimmune Diseases

The collection of commensal bacteria that permanently colonize humans are called the microbiota and its gene content the microbiome. Compared to human cells, the microbiota is believed to be equal in numbers, whereas the microbiome outnumbers the human genome 100-fold. Humans evolved for centuries with their microbiomes and a large body of work supports that the microbiota is involved in the maturation and differentiation of the immune system. Vice versa, multiple immune cells and mediators affect the composition and function of the microbiota.

More recent studies have implicated the microbiota in the pathogenesis of autoimmune diseases. The Kriegel lab is studying how gut and skin commensal bacteria affect lupus and antiphospholipid syndrome using both patient samples and animal models. A growing number of laboratories at Yale are also exploring how the microbiota can affect immune-mediated diseases. The Kriegel lab specifically tests if certain commensals carry bits and pieces that look similar to self-antigens in the body that are targeted in human autoimmune diseases. This process is also called molecular mimicry or cross-reactivity between similar parts in a microbe and the host. As opposed to an infectious agent, the chronic colonization by a cross-reactive commensal could potentially represent not only an initiating but also perpetuating factor that drives chronic autoimmunity. Identifying and manipulating such triggers could theoretically lead to new ways to abort the ongoing autoimmune response in patients with chronic immune-mediated diseases.

Two current studies in the Kriegel lab are testing this hypothesis with samples and swabs from the skin, mouth, stool, and blood of patients and control subjects. All study subjects are remunerated for their efforts. To find out if you are eligible to participate in these studies or to learn more, contact the study coordinators Irene Matos at 203-737-2736, irene.matos@yale.edu or Kristin DeFrancesco at 203-785-3852, kristin.defrancesco@yale.edu. More information can also be found here and at ClinicalTrials.gov (Identifier NCT01787305).

To test a true relationship between commensal bacteria and self-reactivity, the Kriegel lab also uses animal models that resemble the pathogenesis of lupus and antiphospholipid syndrome. These studies include work with animals that are devoid of any microbes, so called germ-free mice that are subsequently colonized with particular microbes to test their effects on immune function. The autoimmune models are also used to ask if certain diets act through the microbiota to protect from lupus and if an exuberant immune response to viral particles that are encoded in our genomes (by so called endogenous retroviruses) are modulated by the microbiota interacting with the host immune cells. These efforts are aimed at finding new ways to prevent or treat systemic autoimmune diseases. The Kriegel lab also studies in humans if certain genes that predispose to autoimmunity affect the composition of the microbiota and thereby the immune function of the host. Taken together, research within the division includes a broad agenda on trying to understand how commensal organisms may affect rheumatic diseases and how this knowledge can be harnessed to develop new strategies to treat them. Further details can be found here.