Credit score: JCI Perception (2025). DOI: 10.1172/jci.perception.194497
Quick bowel syndrome (SBS) is without doubt one of the most difficult circumstances in gastroenterology, affecting sufferers who’ve misplaced important parts of their small gut as a consequence of surgical procedure, illness or congenital abnormalities. Sufferers with SBS usually battle with continual malnutrition and rely closely on parenteral (intravenous) vitamin, which may severely affect their high quality of life and impose a considerable burden on well being care methods.
Though the prognosis of SBS has improved lately, life-threatening problems similar to catheter-related bloodstream infections and liver failure as a consequence of parenteral vitamin stay main considerations.
Glucagon-like peptide-2 (GLP-2) analogs, significantly teduglutide, have emerged as a major breakthrough in treating SBS. These compounds assist sufferers enhance nutrient absorption and cut back their dependence on parenteral vitamin by mimicking the impact of GLP-2, an intestinal hormone chargeable for sustaining intestine well being.
Sadly, whereas their medical effectiveness is well-established, the exact manner during which these remedies work on the mobile degree inside the human physique stays unclear. Extra particularly, the way in which during which these molecules have an effect on the intestine’s epithelial cells and immune cells, in addition to how they affect the intestine microbiome, are largely unknown. Understanding these mechanisms is essential for optimizing present SBS therapies.
To deal with this data hole, a analysis crew led by Assistant Professor Yumi Kudo from the Division of Pediatric Surgical procedure, Faculty of Drugs at Keio College, Japan, performed the primary complete longitudinal examine inspecting how GLP-2 analog remedy transforms the intestinal atmosphere on the mobile degree.
The examine, co-authored by Affiliate Professor Tomohisa Sujino, Professor Akihiro Fujino, and Senior Assistant Professor Yohei Yamada from Keio College, is printed within the journal JCI Perception.
The researchers tracked 5 male sufferers with SBS over a interval of 1 12 months of teduglutide therapy. They collected intestinal tissue biopsies, blood samples, and intestine microbiome samples from the sufferers at three time factors: earlier than the beginning of therapy, at six months into the therapy, and at 12 months into the therapy.
Utilizing single-cell RNA sequencing, the researchers had been in a position to study particular person cells and establish how completely different cell populations modified over time. As well as, they used ribosomal RNA sequencing to observe shifts within the intestine microbiome composition and cell inhabitants over time. This longitudinal strategy supplied detailed insights into the progressive transformations within the intestinal atmosphere through the therapy section.
Their findings revealed an unlimited post-treatment transforming of the intestinal ecosystem. Sufferers confirmed important medical enhancements, together with weight achieve, a decreased want for intravenous vitamin, and elevated ranges of serum biomarkers that point out higher nutrient absorption. On the mobile degree, the researchers found that therapy with GLP-2 analog promoted the enlargement of the villi (nutrient-absorbing buildings) and intestinal crypts.
Furthermore, the inhabitants of regulatory T cells, which assist management irritation, elevated considerably, whereas that of inflammatory Th2 cells decreased. The intestine microbiome additionally turned extra numerous, with larger alpha variety and elevated bacterial manufacturing of short-chain fatty acids, compounds that help intestinal barrier operate and regulate immune responses.
By means of cautious evaluation, the crew discovered that cells that expressed immune-related genes (MCH I/II-expressing Top1 cluster) decreased, whereas cells specialised for nutrient absorption (enterocyte-Top2 and center clusters) expanded. This shift instructed that GLP-2 analog remedy results in helpful variations for sufferers battling malabsorption.
“Our findings indicate that GLP-2 analogs reshape intestinal immunity and microbiota, fostering a less inflammatory environment while promoting nutrient uptake efficiency,” explains Dr. Kudo. “These insights offer a deeper understanding of the role of GLP-2 analogs in gut adaptation and provide a foundation for refining clinical strategies for SBS treatment.”
Notably, these outcomes have necessary implications past SBS. GLP-2 analogs may probably profit sufferers requiring immunosuppression, similar to those that have undergone bone marrow or organ transplantation. By selling a much less inflammatory intestinal atmosphere and enhancing nutrient absorption, these therapies may additionally assist tackle malabsorption points widespread in immunocompromised sufferers.
“To our knowledge, this is the first study to provide human-based evidence supporting the efficacy of GLP-2 analogs. It also represents a rare example of reverse translational research, wherein clinical findings precede and inform subsequent basic research,” concludes Dr. Sujino.
Additional analysis efforts on this course may help make clear the varied results of GLP-2 analogs, solidifying their potential for offering efficient remedies for gastrointestinal and probably immune-related problems.
Extra info:
Yumi Kudo et al, Longitudinal single-cell evaluation of glucagon-like peptide-2 therapy within the sufferers with brief bowel syndrome, JCI Perception (2025). DOI: 10.1172/jci.perception.194497
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Keio College International Analysis Institute (KGRI)
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Longitudinal examine reveals how brief bowel syndrome therapy transforms the gut at a mobile degree (2025, August 27)
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