In a new study published in Nature, researchers from the University of Oslo, Oslo University Hospital and the University of Cambridge have mapped over 1.5 million gut cells.?
The objective is to produce an atlas of all the cells in the gut. In addition, the researchers have made significant discoveries in relation to intestinal diseases such as coeliac disease, ulcerative colitis and Crohn’s, disease. The hope is that it will become possible to offer patients more personalised treatment options.
In Norway, it is estimated that around 50,000 people have coeliac disease, while another 40,000 to 50,000 suffer from inflammatory bowel disease (IBD). IBD consists of ulcerative colitis and Crohn's disease. These conditions are characterised by inflammation in the gut. Common symptoms are belly pain, diarrhea and fatigue.
“Our knowledge of how cells in the gut communicate is limited, so this is very exciting. The aim is to gain a better understanding of how the gut functions when healthy, and what may go wrong in the gut with various intestinal diseases,” Professor Frode Jahnsen at the University of Oslo says.
Aim to understand how cells in a diseased gut behave
In the study, the researchers examined gut cells in healthy individuals as well as in individuals with intestinal diseases. They analysed the cells in far greater detail compared to previous studies.
Between 100 and 120 distinct types of cells populate the gut. The researchers aimed to identify the characteristics of each cell type. How do the cells behave in the gut of healthy individuals compared to in the gut of individuals with an intestinal disease?
“For instance, we investigated which cells a person with Crohn’s disease possesses in their gut. We discovered that cells that appear identical may have quite distinct functions,” Jahnsen says.
“If we can discern which cells drive inflammation within the gut, we can direct our treatments directly towards these target cells,” he explains.?
Found alterations in stem cells in coeliac disease, ulcerative colitis, and Crohn’s disease
Another finding of the study is that stem cells undergo transformations in individuals with intestinal diseases. A stem cell is one that has the potential to evolve into new, more specialised cells through cell division.
The researchers hypothesise that there is a correlation between the inflammation in the gut and the alterations of the stem cells.
“The altered stem cells attract immune cells, such as T-cells. The immune cells are supposed to contribute to the resolution of a disease,” the Professor says.
“Nevertheless, immune cells may inflict more harm than benefit. They seem to be one of the reasons why inflammation—and consequently the disease—persists,” he continues.
May be possible to reduce gut inflammation by blocking the signals between cells
Researcher Raquel Bartolomé-Casado has also contributed to the study. She explains that they aim to study how different cell types within the gut collaborate and communicate with one another.
“Now that we have far greater knowledge about gut cells, we can predict how these cells might communicate. During inflammation, the cells activate each other. If we can identify the signals between the cells, we may be able to block these signals with drugs,” she says.
“This is the same principle that is currently utilised when treating cancer through immunotherapy,” the researcher adds.
Researchers aim to map all cells in the body in The Human Cell Atlas project?
The present study is part of an extensive international collaborative project known as The Human Cell Atlas. The project’s aim is to catalogue all the cells within the human body in an atlas, almost like a Wikipedia of the cells. It builds upon vast datasets collected across numerous countries.
The atlas provides information about the genes expressed in each individual cell.?
“New technology, enabling analysis at the single-cell level, allows us to gather unique information about the cells in all organs of our body,” Bartolomé-Casado says.
The Human Cell Atlas is accessible to researchers and others who wish to utilise the datasets.
“The mapping that we have done of the cells in the gut serves as a reference point for others who seek to study the gut. Other researchers can analyse the same datasets,” Jahnsen points out.
He believes that the project may have substantial implications for research on health and disease in the future.
“I anticipate that this work will influence how we diagnose, prevent, and treat various diseases in the coming years,” the Professor says.
High patient participation in studies?
The data were gathered from patients and healthy controls from studies at the University of Oslo, Oslo University Hospital as well as national and international partner institutions.
Participants from the IBSEN III study on inflammatory bowel disease (IBD), led by Professor Marte Lie H?ivik at the University of Oslo, have been instrumental in providing clinical samples for the research.
“Cell samples from both healthy individuals and patients with various intestinal diseases in Norway have been immensely valuable for the study. Norwegians' willingness to participate in this type of research is crucial for our research efforts,” Jahnsen says.
Towards personalised treatment for intestinal diseases?
The researchers believe that personalised treatment options will become the norm for treating intestinal diseases in the future.?
“The real breakthrough would be if we could provide personalised treatments for patients with intestinal diseases based on the analysis of cell samples. Based on the analysis, we could identify which patients would benefit from which types of treatments,” Jahnsen explains.
“I believe that we will be able to offer more personalised treatments to these patient groups within just two to three years. We might also uncover new targets for treating intestinal diseases,” he says.
The Professor points out that The Human Cell Atlas project is still in its starting phase.
“We need to consider the long-term perspective as well. I believe that there will be dramatic changes in how we treat these patient groups in the future,” Jahnsen concludes.
The study represents a collaborative effort between researchers at the Wellcome Sanger Institute, University of Cambridge, United Kingdom, and researchers at the Jahnsen Lab, University of Oslo and Oslo University Hospital. The work in Cambridge is led by Professor Sarah Teichmann. At UiO and OUS, the study is headed by Professor Frode Jahnsen. Researcher Raquel Bartolomé-Casado completed her doctorate at Jahnsen Lab at the University of Oslo, and was awarded the HM The King's Gold Medal and Professor Kreybergs award for her doctoral work.?
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Reference
Oliver, A. J., Huang, N., Bartolome-Casado, R., Li, R., Koplev, S., Nilsen, H. R., ... & Teichmann, S. A. (2024). Single-cell integration reveals metaplasia in inflammatory gut diseases. Nature, 635(8039), 699-707.?doi: 10.1038/s41586-024-07571-1.?Here you can find the publication.