The role of the microbiome on overall health and on the development of disease is a rapidly growing area of research. Mast cells (MCs) are one of the main cell types that are in direct contact with the microbiome in the gut and given the MCs role within the innate and adaptive immune systems, the interaction between MCs and the microbiome is likely an important factor affecting immune modulation. Autoimmunity is one major consequence of both aberrant mast cell activity and dysbiosis. Using retrospective data, this talk will explore the relationship between the microbiome and mast cells in the development of autoimmune diseases and will present a new approach to treating autoimmune disorders, or knowing what to recognize and when to refer if not within scope. Aims: To understand how mast cells and the microbiome together promote autoimmunity. Patients and Methods: 12 patients between the ages of 12-65 who were evaluated for mast cell activation syndrome and who also showed signs of autoimmunity, either with positive thyroid antibodies, positive ANA or other positive autoantibody, had stool testing performed specifically looking at the microbiome. Results: All 12 patients with autoimmune markers met Consensus-2 criteria for MCAS and all showed abnormal findings on their stool tests, most consistently low levels of short chain fatty acids, such as butyrate, and low or absent levels of Akkermansia muciniphila. The presence of Akkermansia is associated with decreased inflammation and integrity of the intestinal barrier. Low levels are associated with the opposite and likely plays a role in the development of autoimmunity according to recent studies. In this retrospective review all patients had symptoms suggestive of MCAS prior to the development of the autoimmune markers and all had a history and symptoms suggestive of dysbiosis confirmed with stool testing. Treatment with mast cell targeted therapy combined with therapy targeted at improving the microbiota, healing of the intestinal barrier, increasing short chain fatty acids, decreasing bacterial-derived LPS and balancing other metabolic processes, including insulin resistance, had a significant effect on modulating the immune response, mast cell function, and improved patient outcomes. Conclusion: The combination of dysfunctional mast cells with an abnormal microbiota is a risk factor for the development of autoimmunity. Patients with autoimmunity should have their microbiome analyzed and undergo evaluation for mast cell activation syndrome. Treatment should be geared towards both with the goal of improved immune modulation. 

Learning Objectives:

1. Identify factors involved in the disruption of the normal microbiome and discuss how this affects the immune system, and specifically mast cells
2. Describe how crosstalk between abnormal microbiota and aberrant mast cells promotes the development of autoimmunity
3. Discuss the treatment options targeted toward mast cells and the microbiome to achieve immune modulation