Date of Award

Fall 2011

Degree Type

Thesis

Degree Name

Master of Science (MSc)

Department

Medical Sciences

Supervisor

Waliul Khan

Co-Supervisor

John Bienenstock

Language

English

Committee Member

Elyanne Ratcliffe

Abstract

Parasite infections around the world are a huge economic burden and decrease the quality of life for many people. Probiotic bacteria are being investigated as a possible treatment for many enteric issues due to their beneficial effects by altering the immune system. Goblet cells are the main source of mucins in the gut, and play an important role in host defense. Alterations in goblet cells and mucin have been implicated in a number of gastrointestinal (GI) diseases and infections. The aim of this study is to develop a probiotic based strategy to modulate goblet cell function in relation to host defense in enteric infection. Utilizing a murine model of parasite infection, Trichuris muris, we examined the effect of daily administration with probiotic Lactobacillus reuteri in different strains of mice and investigation of goblet cell alterations, immune and inflammatory responses in gut, and host defense mechanisms.

Treatment with live L. reuteri significantly enhanced worm expulsion in resistant C57BL/6 mice and this was associated with significant increase in goblet cells numbers and an increase in IL-10. This lead to investigation of the probiotic effects in IL-10 knock out (KO) and Muc2 KO mice during the infection. There was no difference of worm burden or goblet cell amounts in infected IL-10 KO mice infected treated with probiotic or medium. In infected Muc2 KO mice treated with L. reuteri, there was an earlier increase of goblet cells, and a corresponding decrease in worm numbers. Finally, assessment of this probiotic in susceptible ARK mice revealed no alterations in worm burden, but the treatment prevented the increase in IFN-γ and IL-1β and significantly increased goblet cell numbers.

These data demonstrate that altering the flora with probiotic L. reuteri treatment can modulate intestinal goblet cell biology and immune responses in gut, and promote worm expulsion, possibly through an IL-10 mediated mechanism. The increases in goblet cell numbers may also play a role in the early expulsion of the parasite. In addition to enhancing our understanding on the beneficial effect of probiotics in host defense in enteric infection, this research provides new information on gut function in the context of goblet cells and mucins.

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