Personalised intestinal models

Oral Presentation | Simone Osborne

Date & Time: Friday June 26 2020, 11:55

Abstract

Simone Osborne1, Rama Addepalli1, Ilka Priebe2, Theodora Almond2, Sarron Randall-Demllo2, and Kim Fung3

Affiliations:

  1. CSIRO Agriculture and Food, 306 Carmody Road, St Lucia QLD 4067
  2. CSIRO Health and Biosecurity, Kintore Ave, Adelaide, SA, 5000
  3. CSIRO Health and Biosecurity, 11 Julius Avenue, North Ryde, NSW, 2113

Gastrointestinal processes cannot be easily monitored in vivo, therefore in vitro models have been developed to better understand gastrointestinal processes. In vitro intestinal models have evolved considerably over the last 30 years from adherent two-dimensional (2D) monolayers involving one cell type to more complex three-dimensional (3D) models like intestinal organoid systems. These models can be used to measure toxicity, bioavailability, and metabolism of nutrients, drugs, and other bioactives or non-nutritional molecules in healthy or inflammatory settings. In the pursuit of personalised intestinal models that will better mimic in vivo processes and enable us to understand more about individual variations in gastrointestinal processes, we modified existing 2D models and sought to incorporate intestinal organoids.

To mimic intestinal inflammation associated with many diseases, we modified an existing intestinal co-culture model incorporating enterocytes (Caco-2) and goblet cells (HT29-MTX-E12). Caco-2 and HT29-MTX-E12 cells were grown on semi-permeable transwell membranes for up to 21 days enabling cells to differentiate into a polarised barrier. Following this, cytokines were added to induce changes to the barrier integrity monitored through transepithelial electrical resistance. To determine whether yoghurt made with different protein contents and varying casein and whey ratios could prevent barrier changes induced by inflammation, different yoghurt preparations were digested and applied to the cell model. Yoghurt made with 12% total protein, and 80% casein and 20% whey, prevented barrier changes significantly more than other yoghurt preparations.

Intestinal organoids represent a novel ex vivo model system that incorporates all intestinal cell types, rather than just one or two associated with traditional intestinal models. Organoids are 3D organ “buds” that can be propagated from stem cells and isolated intestinal crypts derived from ex vivo biopsy from humans or animals. However, 3D organ buds are not readily compatible with high throughput screening or for measuring movement of a target molecule across a barrier. To develop a higher throughput 2D model containing intestinal organoids, tissue from mice was collected. Intestinal crypts were liberated from duodenum, jejunum, and ileum tissue and cultured to produce organoids. Activities are now underway to culture mouse intestinal organoids on a 2D membrane. Organoids have also been created from biopsied human intestinal tissue and are being adapted to enable measurement of specific physiological responses using a high throughput screening approach. These enhanced models may help design foods structured to delivering specific nutrients and bioactive molecules to a target demographic, and even individuals, making personalised nutrition more attainable.

Presentation Video

Presenting Author

Simone Osborne

Senior Research Scientist
CSIRO – Agriculture and Food

Dr Simone Osborne is a Senior Research Scientist and Team Leader in the Molecular Analysis Team in CSIRO Agriculture and Food based at the Queensland Bioscience Precinct in Brisbane, Australia. Simone uses in vitro bioassays and biochemical techniques to identify and characterise bioactive molecules from diverse sources including food, processing waste streams, and animal feed.