Giardia duodenalis Depletes Goblet Cell Mucins and Degrades MUC2, Facilitating Bacterial Translocation

Abstract

Giardia duodenalis, a cosmopolitan diarrheagenic parasite of the small intestine, leads to post‐infectious irritable bowel syndrome (PI‐IBS) and extraintestinal complications via unclear mechanisms. The effects of Giardia on the protective mucus layers of the intestine are unknown.ObjectivesC57BL/6 (WT) and Muc2‐/‐ mice, human goblet cell line LS174T, and purified human mucin were exposed to Giardia trophozoites or Giardia's secreted product to assess the effects of Giardia on MUC2 and goblet cell mucins.ResultsInfected Muc2‐/‐ mice had higher parasitic loads and inhibition of weight gain versus WT mice. Goblet cell mucin (stained with PAS/AB and WGA) was depleted in the small intestine and colon of infected WT mice. Bacterial translocation to the liver and spleen was also increased in infected mice. Immunofluorescence staining of MUC2 was reduced in human goblet cells in vitro after exposure to Giardia trophozoites. In addition, a co‐incubation of Giardia's secreted products with purified human mucin degraded MUC2.ConclusionsMUC2 mucin is protective in giardiasis, but Giardia is able to overcome this barrier. While Giardia colonizes the upper small intestine, it induces mucin depletion in goblet cells throughout the small intestine and colon. Mucin depletion and degradation break down the protective mucus barrier, facilitating bacterial translocation. These mechanisms may contribute to PI‐IBS. Supported by HPI NSERC CREATE, NSERC Discovery and Queen Elizabeth II Master's Scholarship