Professor El-Omar has selected Dr Victoria Gudiño PhD and Dr Azucena Salas PhD from Inflammatory Bowel Disease Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic of Barcelona, Barcelona, Spain and Dr Raquel Bartolomé-Casado PhD from the Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway, to do the next #GUTBlog.

The #GUTBlog focusses on the ‘Recent Advances in Basic Science paper “Single-cell omics in inflammatory bowel disease: recent insights and future clinical applications” which was published in paper copy in GUT in August 2025.

The team write:

“Today, over 7 million patients suffer from inflammatory bowel diseases (IBD), which is comprised of ulcerative colitis and Crohn’s disease. Onset often occurs at a young age and frequently lasts a lifetime. Both diseases are characterised by abdominal pain, diarrhea, bleeding, and pronounced fatigue, involving complex interactions among various intestinal cell types, including immune, epithelial, and stromal cells. The mechanisms underlying IBD are not fully understood, yet they often stem from an inappropriate immune response to microbial or self-antigens in genetically predisposed individuals. Traditional research methods, such as bulk transcriptomics, have limitations in providing detailed insights because they average signals across diverse cell types. This restricts the understanding of cellular diversity and complexity within the highly organised intestinal tissue.

Numerous researchers worldwide are now studying IBD by applying single-cell omics, including not only scRNA-seq but also scATAC-seq, scTCR-seq, or scBRC-seq to intestinal cells, which provide expression data at the single-cell level from several thousand cells/sample. These technologies have revolutionised the study of IBD by providing insights on an individual cell level. In particular, single-cell methodologies enable the identification of novel and sometimes rare cell types and provide insights into their potential functions, thereby linking them to disease activity and complications. For instance, by applying these innovations to the study of certain IBD-associated complications, including fibrostenosis, perianal fistulae, complications of the pouch, and creeping fat accumulation, researchers have uncovered novel insights into the mechanisms that can drive their development. Ultimately, this knowledge can support the identification of previously unrecognized therapeutic targets for these hard-to-treat complications.

In this review, we aim to provide the research community with a comprehensive record of the studies performed thus far, synthesizing the main findings and sharing our insights on how these technologies can be leveraged in future research and clinical practice.  One of the most obvious applications of scRNA-seq is the study of the composition of tissues. Indeed, scRNA-seq uncovered a remarkable diversity of intestinal cell types; studies have identified between 60 to 80 unique cell types/states in the intestinal mucosa. In addition, based on the transcriptional signature of each cell type, novel markers were obtained that enabled researchers to track rare cell types across patients, measure shifts in cell abundance across various disease states, and analyse transcriptional changes over time. The insights gained from these analyses are particularly important in understanding cell-specific responses to treatment and identifying the underlying mechanisms of drug failure, which have proven in the past to be undetectable by bulk analysis. Indeed, we believe that, as already shown in two independent prospective studies we discuss, the implementation of single-cell technologies in prospective therapeutic studies will be instrumental in identifying predictors of response and uncovering the mechanisms of resistance to drugs. While the full integration of single-cell technologies into clinical practice is still on the horizon, the groundwork is being laid for more personalized approaches to IBD management. The potential benefits include enhanced diagnostics, monitoring capabilities, and prognosis prediction, which could significantly impact the effectiveness of IBD treatment and patient outcomes.

Besides single-cell omic approaches in cell suspensions, emerging techniques, such as spatial transcriptomics and proteomics, are quickly evolving and will no doubt increase our understanding of cellular interactions and environments in situ, showcasing the potential for translational medicine applications. Although still in its infancy, this field is anticipated to enrich the data available for understanding how cells interact within their native contexts, while exploiting the use of old bio-banked fixed tissue samples.

In conclusion, the study of complex diseases is witnessing a transformative shift with single-cell omics technologies, moving beyond traditional methods to a more precise and individualised understanding of IBDs. As these technologies become more affordable and the necessary analysis pipelines are widely implemented, we anticipate a future in which they will become common practice in research and clinical development.”

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