Intravenous Injection of Endogenous Microbial Components Abrogates DSS-Induced Colitis

Abstract

The etiology of inflammatory bowel diseases (IBD) is largely unknown, but appears to be perpetuated by uncontrolled responses to antigenic components of the endogenous flora. Tolerance to antigenic stimulation can be achieved by exposure to a given antigen in high amounts (high dose tolerance). Colitis induced by feeding of Dextran Sodium Sulfate (DSS) is an often-used animal model mimicking clinical and histological features of human IBD. We investigated whether treatment with high doses of endogenous bacterial components can affect the response to these antigenic components and thus impact the course of the inflammatory response induced by DSS. 129/SvEv mice were injected intravenously in the tail vein with lysates prepared from fecal material of conventionally-raised mice. Control mice received a solution of bacterial antigen-free lysates prepared from fecal material of germ-free mice. Seven days later, colitis was induced in these mice by introducing DSS (3.5%) in the drinking water for 5 days. Onset and course of the inflammatory response was monitored by assessment of weight loss. Mice were sacrificed at day 7 post colitis induction and tested for histopathologic injury, intestinal cytokine release, and systemic response to bacterial antigens. Intravenous injection with fecal lysates reduced intestinal and antigen-stimulated systemic pro-inflammatory cytokine release and prevented DSS-induced weight loss and intestinal injury. Pretreatment with high amount of endogenous bacterial components has a profound tolerogenic effect on the systemic and mucosal immune responses resulting in reduced intestinal inflammation and abrogates colitis-induced weight loss.