For the first time, scientists have grown live cell intestinal models, allowing them to directly observe early stages of celiac. Researchers at Harvard Medical School in Boston used cells from intestinal biopsies to grow small, simplified organoids resembling the small intestine and its lining.
The study compared organoids1 derived from celiac patients and healthy individuals. Scientists also made monolayers: bubbles of live cells with a membrane one cell thick, resembling the gut lining.
Celiac and healthy organoids took different signals from their genetic code in mounting their immune response. The findings corroborated previous understanding of celiac inflammation while revealing new information.
For example, celiac cells did not die faster than normal, but they reproduced more slowly, giving rise to smaller organoids. This suggests how villous atrophy occurs: the flattening of finger-like projections in the gut lining found in celiac. Further study using organoids may reveal why most celiac patients recover fully but about 13% heal poorly on a long-term gluten-free diet.
Celiac monolayers exposed to gluten were more permeable, allowing gluten to cross the membrane by passing between cells. They also produced more markers of inflammation than healthy samples.
More encouraging, when treated with certain gut microbial products, celiac monolayers reduced their inflammatory response. This supports evidence that a disturbed microbiome may lead to celiac, while treatments could be derived from health-inducing microbes.
Van Waffle is a freelance journalist based in Waterloo, Canada, and research editor for Gluten-Free Living. He blogs at vanwaffle.com.
- Freire R, Ingano L, Serena G, et al. Human gut derived-organoids provide model to study gluten response and effects of microbiota-derived molecules in celiac disease. Scientific Reports. 2019;9:7029. doi:10.1038/s41598-019-43426-w.