By merging 25 datasets, scientists have developed the largest integrated cell atlas of the human gut, revealing a new way stomach cells may contribute to Inflammatory Bowel Disease.
Researchers have created the most thorough cell map of the human gut to date by combining spatial and single-cell information from 1.6 million cells.
Understanding the cellular structure of the gut can enhance our knowledge of conditions like bowel cancer and Inflammatory Bowel Disease (IBD). Utilizing this atlas, a team from the Wellcome Sanger Institute and their partners found a new function of a specific gut cell, which may exacerbate a cycle of inflammation in certain individuals, potentially leading to pain and discomfort.
This study, released today (20 November) in Nature, explains how the researchers synchronized over 25 datasets on single cells from the human gastrointestinal (GI) tract, creating the world’s most extensive freely accessible resource for the human gut. The data includes samples from individuals with and without health issues.
With a more comprehensive understanding of the human gut in both health and disease, scientists can identify significant alterations or discrepancies that may trigger diseases such as ulcerative colitis and Crohn’s disease, paving the way for new drug development targets.
This research forms part of a larger collection of over 40 HCA publications in Nature Portfolio journals, marking a significant advancement in understanding the human body. These interrelated studies have illuminated critical components of human development, health, and disease biology, leading to the creation of essential analytical tools and technologies that will aid in the establishment of the Human Cell Atlas1.
The GI tract encompasses various organs involved in digestion that function collectively to absorb nutrients and act as a defense against pathogens. It begins at the mouth and includes organs like the throat, esophagus, stomach, small intestine, large intestine, rectum, and anus.
GI tract disorders affect millions globally. For instance, ulcerative colitis and Crohn’s disease, both forms of IBD, impact more than seven million people worldwide2, with one out of every 123 individuals in the UK suffering from IBD3. Symptoms of IBD can differ among individuals and significantly affect their quality of life, including abdominal pain, diarrhea, rectal bleeding, severe fatigue, and joint issues.
Bowel cancer, or colorectal cancer, originates in the large intestine and ranks as the fourth most common cancer in the UK, with approximately 43,000 new cases each year4. There are around two million cases globally5, with estimates suggesting that one in 17 men and one in 20 women will develop bowel cancer at some point in their lives4.
Given the prevalence of these conditions, numerous single-cell studies have explored the cellular structure of the GI tract in both health and disease, facing challenges due to different methods and labeling systems which can complicate their use by external researchers.
In this new study, the Wellcome Sanger Institute team and collaborators developed an innovative tool to standardize these datasets, creating a unified resource for gut cells accessible to researchers worldwide. This tool could also be adapted for other organs, facilitating additional research.
The researchers combined 25 datasets, forming an atlas of 1.6 million cells that incorporates single-cell and spatial data, enabling scientists to identify the various cells present, their locations, and their interactions with the surrounding environment. The atlas utilized data from tissue samples from individuals without GI issues as well as those with gastric and colorectal cancers, celiac disease, ulcerative colitis, and Crohn’s disease.
The researchers also identified a type of gut cell that could be associated with inflammation. Known as gut metaplastic cells, they typically play a role in repairing the stomach lining. However, the study found these cells bore genetic similarities to other GI cells involved in inflammation. They propose that inflammation in IBD leads to modifications in these metaplastic cells, which actively contribute to ongoing inflammatory responses.
By gaining insights into this cycle of inflammation, it may be possible to discover new strategies to prevent or treat IBD and potentially apply these findings to other tissues and conditions.
The Gut Cell Atlas is available for free, and the research team has established new procedures to allow for ongoing additions, creating an ever-evolving, accessible resource for scientists.
Dr. Amanda Oliver, the lead author from the Wellcome Sanger Institute, stated: “The combination of spatial and single-cell data reveals unique insights into how gut cells interact, which can help build a deeper understanding of human physiology. Merging existing datasets allows us to construct a richer view of the human gut, fostering collaboration among researchers to advance human health. Our Gut Cell Atlas, being harmonized and freely accessible, is designed to encourage contributions from others that can be utilized by scientists globally.”
Dr. Rasa Elmentaite, co-senior author formerly at the Wellcome Sanger Institute and currently at Ensocell Therapeutics, commented: “The comprehensive nature of this integrated atlas, which includes data from individuals both with and without gut disorders, has allowed us to identify a pathogenic cell type that may be implicated in certain chronic conditions, presenting a potential target for future interventions. This illustrates the effectiveness of integrated single-cell atlases in research, and I am optimistic that applying this method to other tissues and organs will lead to significant therapeutic breakthroughs for various conditions.”
Professor Sarah Teichmann, co-senior author and co-founder of the Human Cell Atlas, formerly at the Wellcome Sanger Institute and now at the Cambridge Stem Cell Institute, said: “A nuanced understanding of cells through the Human Cell Atlas will clarify many aspects of human health and disease and could unveil new treatment pathways. This harmonized Gut Cell Atlas exemplifies what can be accomplished through collaborative efforts among scientists worldwide and has resulted in a comprehensive resource that everyone can use to seek new methods for understanding and treating diseases.”
The Gut Cell Atlas resource can be accessed here: https://www.gutcellatlas.org/
- The HCA is a global collaborative consortium aiming to create extensive reference maps of all human cells—the essential units of life—to enhance our understanding of human health and improve disease diagnosis, monitoring, and treatment. The HCA community is assembling high-quality atlases of various tissues, organs, and systems to construct a comprehensive Atlas of the human body. Over 3,500 HCA members from more than 100 countries are collaborating to develop a diverse and accessible Atlas that benefits humanity globally. Discoveries made through this initiative are informing medical applications from diagnostics to drug discovery, and the Human Cell Atlas will impact all areas of biology and healthcare, signaling a new era of precision medicine. https://www.humancellatlas.org
- V. Jairath, B. G. Feagan. (2020) Global burden of inflammatory bowel disease. The Lancet. DOI: 10.1016/S2468-1253(19)30358-9
- New research shows over 1 in 123 people in the UK living with Crohn’s or Colitis. (2022) Crohn’s & Colitis UK, available at: https://crohnsandcolitis.org.uk/news-stories/news-items/new-research-shows-over-1-in-123-people-in-uk-living-with-crohn-s-or-colitis [Accessed July 2024]
- Bowel cancer. (reviewed June 2024) Bowel Cancer UK, available at: https://www.bowelcanceruk.org.uk/about-bowel-cancer/bowel-cancer/ [Accessed November 2024]
- E. Morgan, M. Arnold, A. Gini, et al. (2023) Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut. DOI: 10.1136/gutjnl-2022-327736.
