Novel insights in post‐infectious irritable bowel syndrome in experimental giardiasis (650.15)

Abstract

Giardia duodenalis infections can lead to post‐infectious irritable bowel syndrome (PI‐IBS), a disorder characterized by chronic visceral pain. Using a new model of post‐giardiasis IBS, this study aimed to reveal novel mechanisms responsible for PI‐IBS. Weaning rats were gavaged with live Giardia trophozoites (assemblages A or B). Visceral hypersensitivity was assessed 50 days post‐infection (DPI) by measuring blood pressure changes in response to jejunal/rectal balloon distension. Spinal cord expression of c‐fos was used as a marker of nociceptive signaling. Caco‐2 monolayers were used to assess non‐invasive E. Coli HB101 translocation, as well as the integrity of epithelial barrier structure and function at early time points. c‐fos activation was observed during the acute phase. While the infection was cleared by 21DPI, jejunal and rectal hypersensitivity was observed 50 DPI with either assemblage along with mast cell infiltration. In vitro challenge with Giardia also facilitated the paracellular translocation of E. coli, increased epithelial permeability, and disrupted the tight junctional (TJ) proteins occludin and claudin‐4. These data show that Giardia‐induced IBS is associated with TJ proteins disruption, translocation of a commensal E. coli and c‐fos activation during the acute phase of the infection, as well as mast cell infiltration and visceral hypersensitivity. Findings in this model will help identify the mechanisms of Giardia leading to post‐giardiasis‐IBS.Grant Funding Source: Supported by the French ministry of secondary education and research, NSERC‐CREATE