Bestowing scientists with better knowledge of what happens in conditions such as bowel cancer and inflammatory bowel disease (IBD) is mapping the cells in the gut. Using this atlas, the Wellcome Sanger Institute and its collaborators discovered a new function of one type of gut cell in the inflammation cycle, which could cause pain and distress in some people.
The study, published in Nature Today, shows how the team harmonized over 25 human GI tract single-cell datasets to create the world’s largest free resource of the human gut to date. The samples included individuals with health conditions and those without. To understand the human gut in depth researchers need to observe the differences or mandatory changes that act as a fuel for conditions like ulcerative colitis and Crohn’s disease.Â
This is one of a collection of more than 40 Human Cell Atlas publications in journals in Nature Portfolio that represent a milestone leap forward in how we understand the human body. Millions of lives are affected by GI tract conditions annually. 
Colorectal cancer, also referred to as bowel cancer, is the fourth most common type of cancer in the UK, and one in every 17 men and one in every 20 women will be diagnosed with bowel cancer. The processes and labeling systems are separate in these studies which can present difficulties when external researchers try to use them.
The latest study saw researchers from the Wellcome Sanger Institute and collaborators design a new tool to bring these data into a unified resource so that they mean the same thing to everyone and are available to researchers across the world. It could also be applied to other organs to facilitate further studies.
The researchers created the Atlas, using tissue samples from individuals without gastrointestinal issues and from those with gastric or colorectal cancer, ulcerative colitis, and Crohn’s disease. The gut metaplastic cells are known to play a role in healing the lining of the stomach. However, the team learned that these cells were genetically reminiscent of other GI cells known to participate in inflammation.
In its place, they hypothesize that IBD-related inflammation causes the changes in metaplastic cells that actively drive further inflammatory responses. It’s freely available, and the team has designed new processes so that future studies can be added, and the resource evolves into an evolving, open-access resource for scientists.
By combining existing single-cell datasets we create a better picture of the human gut and allow researchers to work together to better human health. “We also publish and make ours a harmonized Gut Cell Atlas freely available, and we hope people will continue to build on this and add in data for it to be used by scientists all around the world.”
This integrated atlas contains such a large number of data generated from individuals with or without gut diseases, which allowed us to identify a pathogenic cell type that may contribute to chronic conditions and is a potential target for future intervention, said Dr. Rasa Elmentaite, previously at the Wellcome Sanger Institute and now at Ensocell Therapeutics, co-senior author.
“This shows how powerful it is to use integrated single-cell atlases in research, and I would expect that similar applications to other tissues and organs will reveal new therapeutic discoveries for a tremendous number of conditions.”
“This harmonized Gut Cell Atlas illustrates what can be achieved through open collaboration with worldwide scientists and thus provides an accessible combined resource for anybody to use and discover new avenues of disease understanding and treatment.”
Reference: Oliver AJ, Huang N, Bartolome-Casado R, et al. Single-cell integration reveals metaplasia in inflammatory gut diseases. Nature. 2024;635(8039):699-707. doi:10.1038/s41586-024-07571-1
