Treatment with an orally delivered non-replicating, non-colonizing strain of Veillonella parvula resolves systemic inflammation in murine models of disease

Introduction The mucosal immune system comprises of a complex network of intestinal epithelial cells and immune cells. We report that an orally delivered microbial strain of Veillonella parvula (EDP1867) that is non-replicating and non-colonizing acts through pattern recognition receptor mediated modulation of small intestinal immune responses to induce potent systemic inflammation resolution. Methods EDP1867 is a strain of Veillonella parvula isolated from mucosal tissue of a human donor and rendered non replicating by gamma irradiation. In vitro experiments were performed in primary human immune cells. In vivo efficacy was done using mouse models of delayed-type hypersensitivity (DTH) and psoriasis. Fluorescently labeled EDP1867 was used in biodistribution experiments. Results EDP1867 induced IL-10 in primary human immune cells. In a DTH model, orally delivered EDP1867 reduced inflammation and diminished production of pro-inflammatory cytokines ex vivo. Fluorescently labeled EDP1867 transited through the gut without systemic exposure in biodistribution studies to demonstrate gut restriction. EDP1867 activity is dependent on TLR2 and migration of immune cells through the gut. In an imiquimod-induced psoriasis model, EDP1867 reduced skin inflammation and psoriasis score and Th17 cytokines in the skin. Conclusions EDP1867 drives broad based resolution of inflammation and can reestablish normal homeostasis. These data demonstrate that EDP1867 can act as a new oral anti-inflammatory drug that is gut restricted and dependent on local immune recognition within the small intestine, to induce systemic anti-inflammatory effects. EDP1867 is currently in clinical development for treatment of inflammatory diseases.