Label-free and targeted mass tandem (TMT-labelled) global proteomic analyses on mucus from the stomach, small and large intestine of pigLabel-free and targeted mass tandem (TMT-labelled) global proteomic analyses on mucus from the stomach, small and large intestine of pig

The gastrointestinal mucus is a hydrogel that lines the luminal side of the gastrointestinal epithelium, offering barrier protection from pathogens and lubrication of the intraluminal contents. These barrier properties likewise affect nutrients and drugs that need to penetrate the mucus to reach the epithelium prior to absorption. In order to assess the potential impact of the mucus on drug absorption, we need information about the nature of the gastrointestinal mucus. Today, most of the relevant available literature is mainly derived from rodent studies. In this work, we used a larger animal species; the pig model to characterize the mucus throughout the length of the gastrointestinal tract. This is the first report of the physiological properties (physical appearance, pH and water content), composition and structural profiling of the porcine gastrointestinal mucus. Gastrointestinal mucus was collected from the stomach, small intestine (duodenum, jejunum, ileum) and large intestine (cecum, proximal and distal colon) from slaughtered pigs. The composition of the mucus was characterized both with labelfree and TMT proteomics, with lipidomics and metabolomics. The structural profiling was determined with rheological measurements and cryo-Scanning Electron Microscopy. These findings allow for direct comparisons between the characteristics of mucus from various segments and can be further utilized to improve our understanding of the role of the mucus on region dependent drug absorption. Additionally, the present work is expected to contribute to the assessment of the porcine model as a preclinical species in the drug development process.