Effects of Deoxynivalenol and grain components on the gut and immune system

The integrity of the intestine depends on tight regulation of the mucus layer, tight junctions, epithelial cells and the host innate and adaptive immune response. Goblet cells reside throughout the gastrointestinal tract (GI) and are responsible for the production of mucus. The mucus layer provides the first line of defense against physical and chemical injury caused by ingested food and microbes.

Deoxynivalenol (DON) is a mycotoxin present in practically all samples of grain-based food. The dietary intake of DON in children exceeds the current TDI. Indications of inflammations in the GI and brain were found in mice given oral doses similar to the exposure in Norwegian children. Low doses of DON have also been associated with increased permeability of the GI (“leaky gut”). Grain also contains other compounds affecting the GI, like beta-glucans, gluten and LPS, a component of the bacterial cell wall known to trigger an inflammatory response of the immune system.  Low-dose exposure to DON also induces pro-inflammatory effects. The initiating mechanism is probably inhibition of the protein synthesis. Simultaneously, DON increases release of pro-inflammatory cytokines involved in immunity and inflammation. DON may also reduce the intestinal mucus production. On the other hand, other compounds in grain may protect the gut. Increasing dietary oat fibre decreases the permeability of intestinal mucus and beta-glucans has been found to increase mucin (the key protective components of the mucus) expression in human airway epithelial cells.

Hypothesis: DON affects the mucus production, immune response and permeability in the gut. The effects are modulated by other compounds in grain such as LPS, beta-glucans and gliadin.

Methods: Test system: Human gut epithelial, goblet and mucus producing cells and macrophages. We will first screen for effects of DON and other bioactive compounds present in grain such as beta-glucans, gliadin and other mycotoxins (alone and in combination) induced cytotoxicity. DON and beta-glucans (alone and in combination) will then be used to investigate the production of mucus (Alcian Blue staining) and/or its effects on protein expression of mucins (flow cytometry/confocal microscopy). Furthermore, we will study the effects of the compunds on the integrity of the epithelial layer expression of tight junction proteins and permeability

Expected outcome: One thesis for Master of Science, results that can be a main part of a scientific paper published by the Norwegian Veterinary Institute (NVI) and increased knowledge of effects of Fusarium infected grain on the gastrointestinal tract.

Organization: The work will be carried out at NVI, Oslo. The project will require continuous work on the lab and the student will be followed closely by the supervisors at NVI.  We are looking for a student who enjoys working in the lab. Supervisors: Senior Scientist Anita Solhaug and Senior Scientist Gunnar Sundst?l Eriksen. Toxinology research group, NVI.

Contact: Gunnar.eriksen@vetinst.no or Anita.solhaug@vetinst.no

Published Apr. 19, 2018 8:14 AM - Last modified July 16, 2018 2:16 PM

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