Researchers have created the most comprehensive map yet of all the cells in our gut. This atlas is intended to help understand what exactly happens with diseases such as colon cancer or inflammatory bowel disease. For example, using this atlas, researchers have already discovered that certain intestinal cells contribute to an inflammatory cycle that causes painful gastrointestinal symptoms in some people. This knowledge could be used to develop new diagnostic methods and active ingredients in the future. The Intestinal Atlas is part of a larger atlas that covers the entire human body.
The gastrointestinal tract includes all stations of the digestive system, from the mouth, throat and esophagus to the stomach, small and large intestines, rectum and anus. These organs work together to absorb nutrients from our food and remove waste products. At the same time, the gastrointestinal tract serves as a barrier against pathogens and plays an important role in our health.
However, millions of people worldwide suffer from diseases of the gastrointestinal tract such as stomach or colon cancer, celiac disease or the chronic inflammatory bowel diseases ulcerative colitis and Crohn’s disease. Symptoms of the disease often include abdominal pain, diarrhea, bleeding from the anus, extreme fatigue and joint problems. In order to understand what happens at the cellular level in the intestine during these diseases, researchers have already carried out numerous independent studies. However, they usually only looked at individual cell types and clinical pictures and used different methods. This makes it difficult to compare and summarize the results.
Atlas of all intestinal cells
A team led by Amanda Oliver from the British Wellcome Trust Sanger Institute has now evaluated 25 such individual studies on the gastrointestinal tract in detail and summarized them in a standardized manner. The individual studies contained data on the characteristics of a total of 1.6 million intestinal cells from the tissue of sick and healthy people, children and adults. This has now resulted in the most comprehensive map of our intestines to date. The atlas marks which cells are where and how they interact with each other. “Spatial and single-cell data provide unique information about how intestinal cells interact, which can be used to gain a deep understanding of how the human body works,” explains Oliver. The atlas is public, so researchers worldwide now have a complete picture of the human intestine for the first time. From this they can better than before identify changes or differences that could be involved in the occurrence of intestinal diseases.
For example, Oliver and her colleagues identified a type of small intestinal cell that could play a role in inflammation in the intestine: metaplastic epithelial cells that transform into other epithelial cells. This form of conversion is actually involved in the healing of the stomach lining. However, the team discovered that these cells in the small intestine shared genetic similarities with glandular cells in the stomach and duodenum, which have been shown to be involved in inflammation. Based on their data, Oliver and her colleagues suspect that in such intestinal diseases the stem cells in the small intestine change into metaplastic cells, which then trigger the immune system via messenger substances and thus promote further inflammatory reactions. This leads to an inflammatory chain reaction.
Hope for better diagnostic methods and new medications
Based on this, researchers can now study this inflammatory cycle in more detail and look for new ways to treat inflammatory bowel disease. This knowledge could then be used to develop new diagnostic methods and medications. “We were able to uncover a pathogenic cell type that could play a role in some chronic diseases and could be a target for interventions in the future,” says Oliver’s colleague Rasa Elmentaite.
The team hopes that the findings could then potentially be transferred to other tissues and diseases. “This harmonized gut cell atlas has resulted in an accessible combined resource that can be used by anyone to find new ways to understand and treat disease,” says senior author Sarah Teichmann, also from the Wellcome Trust Sanger Institute.
The Intestinal Atlas is part of a collection of more than 40 publications that similarly provide detailed maps of different body parts, tissues and organs. These studies, written by over 3,500 researchers, complement each other and collectively form an atlas of all the cells in the human body. This “Human Cell Atlas” is intended to serve as a reference value for researchers worldwide and to help them find out more about human development and various diseases. Future individual studies should then also be included in the partial atlases such as the intestinal atlas.
Source: Amanda Oliver (Wellcome Trust Sanger Institute) et al., Nature, doi: 10.1038/s41586-024-07571-1; Good Cell Atlas