Molecular changes of the intestinal mucus layer composition during zinc deficiency: (Sub)cellular processing and O-glycosylation of mucins

• Applicant: Dr. Maria Maares
• Subject Area: Nutritional Sciences
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465237366

The essential trace element zinc (Zn) plays an important role for various biological processes in the human body. Approximately 1 billion people worldwide suffer from zinc deficiency, with severe consequences for their well-being, such as impaired intestinal health. In addition to an extreme degeneration of the intestinal epithelium and increased intestinal inflammation, the intestinal mucus barrier is critically disturbed. Yet, the cellular mechanisms leading to the altered mucin and O-glycan synthesis during Zn deficiency as well as the role of Zn for mucin synthesis in the intestine remain elusive. There is strong evidence that the absence of Zn alters the expression of several glycogenes in goblet cells and thrives inflammatory processes that impact the syntheses of MUC2, the main intestinal secreted mucin, on the transcriptional and post-translational level. To this end, this project aims to study Zn-dependent changes of the human glycome as well as to examine the (sub)cellular MUC2 synthesis, processing, and the effect of the (pro)inflammatory cytokine IL-8 on mucin secretion and O-glycosylation using in vitro human Zn-deficient (ZD) goblet cells. Moreover, a ZD mice model will be used to additionally study the impact of the dietary Zn status on the mucus composition in vivo. This project will illuminate the underlying regulatory mechanisms that degenerate the intestinal mucus layer and intestinal health after prolonged Zn malnutrition and will contribute to our understanding of Zn for the human glycome in general.

• DFG Programme: Research Grants