A research team led by Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, has published a comprehensive review in ExRNA that sorts out the diverse roles of extracellular vesicle-associated RNAs (EV-RNAs) in the development and progression of inflammatory bowel disease (IBD). By integrating the latest findings from multi-omics studies and animal experiments, the review points out that EV-RNAs can serve as non-invasive biomarkers for early IBD detection and disease monitoring, and also hold great potential as targets for next-generation targeted therapies. This work provides a solid theoretical basis for advancing personalized precision treatment for the millions of IBD patients worldwide suffering from this chronic recurrent gastrointestinal disorder.
IBD is a lifelong, recurrent inflammatory condition affecting the gastrointestinal tract, and has become a growing global public health concern. It mainly includes two types: Crohn's disease (CD), which causes transmural inflammation that can involve any part of the digestive tract, and ulcerative colitis (UC), characterized by continuous superficial inflammation limited to the colorectal mucosa. Over the past few decades, its incidence has been rising rapidly in both industrialized and newly industrialized countries. It is predicted that by 2045, the prevalence of IBD in early-industrialized regions will exceed 1% of the population.
For IBD patients, recurrent symptoms such as abdominal pain, diarrhea and weight loss often disrupt their daily lives and seriously affect their quality of life. Current clinical management still faces long-standing challenges: diagnosis relies heavily on invasive endoscopic examinations; conventional anti-inflammatory drugs and biological therapies often bring systemic side effects, and many patients eventually develop drug resistance and lose response to treatment. Therefore, there is an urgent and unmet need for more accurate non-invasive diagnostic tools and safer, more targeted treatment strategies.
Against this background, a research team led by Professor Xiyang Wei from the Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, in cooperation with researchers from Zhejiang Chinese Medical University, has conducted a systematic and in-depth summary of the rapidly developing field of EV-RNA research in IBD. This work integrates cutting-edge findings from hundreds of recent studies, comprehensively showing how EV-RNAs regulate core processes related to IBD and their potential for clinical translation.
"Extracellular vesicles (EVs) are like tiny membrane-bound 'biological packages' secreted by almost all types of cells," explained Professor Wei, the corresponding author of the study. "These nanoscale packages contain a variety of RNA molecules, especially non-coding RNAs such as microRNAs and long non-coding RNAs. These EV-RNAs act as key messengers for intercellular communication, shuttling between intestinal epithelial cells, immune cells and even gut microbes to regulate the intestinal microenvironment. Our work integrates the latest global research to clarify how these molecules function in IBD and how we can use them to improve patient treatment."
The team's summary shows that EV-RNAs are involved in multiple core pathological processes of IBD. Pathogenic EV-RNAs can trigger excessive inflammatory responses, damage the intestinal epithelial barrier (often called "leaky gut"), and disrupt the balance of gut microbiota, thereby aggravating disease progression. On the contrary, beneficial EV-RNAs can alleviate inflammation, repair damaged intestinal tissue and restore mucosal homeostasis, showing strong therapeutic potential.
Notably, the review also emphasizes the systemic role of gut-derived EV-RNAs in inducing extraintestinal complications of IBD. Beyond the gastrointestinal tract, IBD is often associated with liver injury and cardiac dysfunction, which significantly increase patient morbidity. The team found that EV-RNAs secreted by inflamed intestinal tissues can enter the bloodstream and reach distant organs, directly regulating inflammatory responses in the liver and heart. This reveals a key molecular mechanism underlying these systemic complications.
One of the most promising clinical applications of EV-RNAs highlighted in this work is their use as non-invasive diagnostic biomarkers. Unlike traditional invasive endoscopy, EV-RNAs are stably protected by vesicles from degradation and can be reliably detected in easily accessible biological fluids such as plasma and even saliva. The review cites multiple clinical studies showing that specific EV-RNA signatures, such as elevated levels of long non-coding RNA H19 in plasma EVs, can distinguish active IBD from disease remission with extremely high accuracy, with area under the curve (AUC) values ranging from 0.95 to 0.97. Even salivary EV-derived microRNA panels have shown good diagnostic performance, providing a truly non-invasive and patient-friendly tool for early screening and real-time monitoring of disease activity.
In terms of treatment, the review outlines a variety of EV-RNA-based therapeutic strategies that have shown remarkable effects in preclinical IBD models. For example, mesenchymal stem cell-derived EVs (MSC-EVs) carry a variety of immunomodulatory miRNAs, which can suppress excessive inflammation, promote intestinal barrier repair and alleviate colitis in animal models. Compared with whole-cell stem cell therapy, these cell-free EVs have a much lower risk of immune rejection and tumorigenesis, making them safer therapeutic candidates.
More notably, the team points out the potential of dietary and plant-derived EVs as oral therapeutic platforms. EVs extracted from natural sources such as bovine colostrum, Coptis chinensis, Centella asiatica and tea contain functional miRNAs that can survive the harsh acidic environment of the gastrointestinal tract, directly target inflamed intestinal tissues and exert anti-inflammatory effects. For instance, EVs from Coptis chinensis deliver a specific miRNA that restores zinc homeostasis in immune cells, thereby inhibiting neutrophil-induced intestinal tissue damage; while bovine colostrum EVs carry a miRNA that blocks the core NF-κB inflammatory signaling pathway. These natural plant-derived EVs provide a patient-friendly oral treatment option with minimal systemic side effects, opening up a new path for adjuvant therapy of IBD.
The review also mentions that engineered EVs represent another cutting-edge direction. Researchers can now modify EVs to display targeting molecules on their surface and load specific therapeutic RNAs, enabling precise and personalized delivery to inflamed intestinal tissues. In preclinical models, these engineered EVs have shown synergistic therapeutic effects: they can not only suppress the activation of pathogenic T cells, but also deliver regulatory RNAs to correct disease-causing molecular defects, bringing new hope to patients with refractory IBD who do not respond to conventional therapies.
The team also acknowledges the key challenges that need to be overcome to translate these promising findings into clinical practice. A major obstacle is the lack of standardized protocols for EV isolation, purification and RNA detection, which leads to inconsistencies in study results across different laboratories. In addition, large-scale multi-center clinical trials are needed to verify the diagnostic and therapeutic efficacy of EV-RNAs in human patients, and clear regulatory pathways for EV-based therapeutics are also required.
"For millions of IBD patients, this field is developing rapidly, and EV-RNAs are at the forefront of this progress," Professor Wei added. "Our review integrates all the latest evidence to show that these molecules are not just passive bystanders in the disease, but core regulators that can be targeted for both diagnosis and treatment. We hope this work will guide future research, accelerate the translation of these discoveries from the laboratory to the clinic, and ultimately bring more effective and personalized treatment to IBD patients around the world."
Although further research and standardization are needed, this comprehensive review marks an important step forward in understanding the role of EV-RNAs in IBD, and opens up new possibilities for transforming the diagnosis, monitoring and treatment of this chronic gastrointestinal disorder.
This paper From biomarkers to therapeutics: extracellular vesicle RNA as a pivotal player in inflammatory bowel disease management was published in ExRNA.
Citation: Ren R, Xu M, Jiang X, Wei X. From biomarkers to therapeutics: extracellular vesicle RNA as a pivotal player in inflammatory bowel disease management. ExRNA 2026(1):0003, https://doi.org/10.55092/exrna20260003.
