Effects of fructans on intestinal immunomodulation and the role of toll-like receptors in Giardia-host immunomodulation - PhDData

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Effects of fructans on intestinal immunomodulation and the role of toll-like receptors in Giardia-host immunomodulation

The thesis was published by Fernández Lainez, Cynthia, in January 2023, Rijksuniversiteit Groningen.

Abstract:

Consumption of dietary fibers (DFs) is associated with a lower risk to develop non-communicable diseases such as irritable bowel syndrome. It is also associated to healthy aging. An important group of DFs are fructans. Fructans are fructose-based polysaccharides, which are mainly extracted from plants. Fructans from chicory roots are widely used in Europe as a source of DFs for food supplementation. In Latin America, endemic plants such as agave represent a rich source of fructans. The mechanisms that underly fructans health beneficial effects are not completely understood. Therefore, in the present thesis we studied the effects of fructans from chicory and agave at the intestinal epithelial barrier function, and at the intestinal immune system. To that end, we performed in vitro studies with intestinal and immune cells, which were exposed to chicory and agave fructans of different length. The experiments were performed under physiological and under induced inflammatory conditions. We found that agave fructans possess a strong anti-inflammatory effect via a group of molecules named Toll-like receptors. We also found that both chicory and agave fructans can protect the epithelial intestinal barrier from the disruptive action of chemical compounds that impair the intestinal barrier. All these results were dependent of the fructan type, as well as of their chain length. Our findings contribute to the knowledge of the mechanisms that underly the beneficial health effects of fructans, which could aid in the design of specific therapies for the prevention and treatment of intestinal inflammatory disorders. In the second part of the thesis, we studied the influence of the enzyme arginine deiminase (GlADI) from the intestinal parasite Giardia lamblia, which is one of the leading causes of diarrhea worldwide. We found that GlADI is able to activate the Toll-like receptors in a dose dependent manner, the 3D structure of GlADI is also fundamental for its action. These results contribute to the knowledge of the crosstalk between the human host and the parasite, which could aid in the proposal of new anti-giardiasic therapies, especially for those Giardia strains that are resistant to the first line drugs.



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