If you eat chili, your gut might revolt, but your friend can eat anything and feel great. You can pop ibuprofen like candy with no ill effects, but your friend’s belly might bleed and might get no pain relief.
The quick answer is because we’re all different. The next questions are how different exactly, and what do these differences mean for health and disease? Answering these is much more difficult, but the United Nation’s School of Medicine lab is revealing some interesting scientific answers by creating the first genetic map of human gut ever.
For the first time, the lab used entire human GI tracts from three organ donors to show how cell types differ across all regions of the intestines, to shed light on cellular functions, and to show gene expression differences between these cells and between individuals.
For this study published Feb. 19 in the journal Cellular and Molecular Gastroenterology and Hepatology, the researchers focused on the epithelium: the single-cell thick layer separating the inside of the intestines and colon from everything else.
Like other cell populations and the microbiota, the epithelium is incredibly important to human health, and for years scientists have been exploring it. But until now, researchers could only take tiny biopsies the size of grains of rice from a few parts of the digestive tract, usually from the colon or limited regions of the small intestine.
“Such exploration would be like looking at the United States from space but only investigating what’s going on in Massachusetts, Oklahoma, and California. We’d want to see everything and studying the gut samples we took from the donors helped us to do that,” said lead author on the study, Scott Magness in a paper.
Using sequencing technology to characterize gene expression, the team first extracts RNA from each cell while keeping each cell separate, and then they run single-cell sequencing, which takes a snapshot of which genes each intestinal cell is expressing and how much.
“The picture we get from each cell is a mosaic of all the different types of genes the cells make, and this complement of genes creates a signature to tell us what kind of cell it is and potentially what it is doing. Is it a stem cell or a mucous cell or a hormone-producing cell or an immune-signaling cell?” Magness said.
“We were able to see the differences in cell types throughout the entire digestive tracts, and we can see different gene expression levels in the same cell types from three different people. This is how we might begin to understand why some people form toxicity to certain foods or drugs and some people don’t,” he added.
