Longitudinal Study Reveals How Glp-2 Analog Therapy Transforms The Intestinal Environment

Short bowel syndrome (SBS) represents 1 of nan astir challenging conditions successful gastroenterology, affecting patients who person mislaid important portions of their mini intestine owed to surgery, disease, aliases congenital abnormalities. Patients pinch SBS often struggle pinch chronic malnutrition and dangle heavy connected parenteral (intravenous) nutrition, which tin severely effect their value of life and enforce a important load connected healthcare systems. Although nan prognosis of SBS has improved successful caller years, life-threatening complications specified arsenic catheter-related bloodstream infections and liver nonaccomplishment owed to parenteral nutrition stay awesome concerns.

Glucagon-like peptide-2 (GLP-2) analogs, peculiarly teduglutide, person emerged arsenic a important breakthrough successful treating SBS. These compounds thief patients amended nutrient absorption and trim their dependence connected parenteral nutrition by mimicking nan effect of GLP-2, an intestinal hormone responsible for maintaining gut health. Unfortunately, while their objective effectiveness is well-established, nan precise measurement successful which these treatments activity astatine nan cellular level wrong nan quality assemblage stay unclear. More specifically, nan measurement successful which these molecules impact nan gut's epithelial cells and immune cells, arsenic good arsenic really they power nan gut microbiome, are mostly unknown. Understanding these mechanisms is important for optimizing existent SBS therapies.

To reside this knowledge gap, a investigation squad led by Assistant Professor Yumi Kudo from nan Department of Pediatric Surgery, School of Medicine astatine Keio University, Japan, conducted nan first broad longitudinal study examining really GLP-2 analog therapy transforms nan intestinal situation astatine nan cellular level. The study, co-authored by Associate Professor Tomohisa Sujino, Professor Akihiro Fujino, and Senior Assistant Professor Yohei Yamada from Keio University, will beryllium published successful nan diary JCI Insight connected September 23, 2025.

The researchers tracked 5 antheral patients pinch SBS complete a play of 1 twelvemonth of teduglutide treatment. They collected intestinal insubstantial biopsies, humor samples, and gut microbiome samples from nan patients astatine 3 clip points: earlier nan commencement of treatment, astatine six months into nan treatment, and astatine 12 months into nan treatment. Using nan method of single-cell RNA sequencing, nan researchers were capable to analyse individual cells and place really different compartment populations changed complete time. In addition, they utilized ribosomal RNA sequencing to show shifts successful nan gut microbiome creation and compartment organization complete time. This longitudinal attack provided elaborate insights into nan progressive transformations successful nan intestinal situation during nan curen phase.

Their findings revealed a immense post-treatment remodeling of nan intestinal ecosystem. Patients showed important objective improvements, including weight gain, a reduced request for intravenous nutrition, and accrued levels of serum biomarkers that bespeak amended nutrient absorption. At nan cellular level, nan researchers discovered that curen pinch GLP-2 analog promoted nan description of nan villi (nutrient-absorbing structures) and intestinal crypts. Moreover, nan organization of regulatory T cells, which thief power inflammation, accrued substantially, while that of inflammatory Th2 cells decreased. The gut microbiome besides became much diverse, pinch higher alpha diverseness and accrued bacterial accumulation of short-chain fatty acids, compounds that support intestinal obstruction usability and modulate immune responses.

Through observant analysis, nan squad recovered that cells that expressed immune-related genes (MCH I/II-expressing Top1 cluster) decreased, while cells specialized for nutrient absorption (enterocyte-Top2 and mediate clusters) expanded. This displacement suggested that GLP-2 analog therapy leads to beneficial adaptations for patients struggling pinch malabsorption. "Our findings bespeak that GLP-2 analogs reshape intestinal immunity and microbiota, fostering a little inflammatory situation while promoting nutrient uptake efficiency," explains Dr. Kudo. "These insights connection a deeper knowing of nan domiciled of GLP-2 analogs successful gut adjustment and supply a instauration for refining objective strategies for SBS treatment."

Notably, these results person important implications beyond SBS. GLP-2 analogs could perchance use patients requiring immunosuppression, specified arsenic those who person undergone bony marrow aliases organ transplantation. By promoting a little inflammatory intestinal situation and enhancing nutrient absorption, these therapies could besides thief reside malabsorption issues communal successful immunocompromised patients. "To our knowledge, this is nan first study to supply human-based grounds supporting the efficacy of GLP-2 analogs. It besides represents a uncommon illustration of reverse translational research, wherein objective findings precede and pass consequent basal research," concludes Dr. Sujino.

Further investigation efforts successful this guidance tin thief explain nan various effects of GLP-2 analogs, solidifying their imaginable for providing effective treatments for gastrointestinal and perchance immune-related disorders.

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Journal reference:

Kudo, Y., et al. (2025). Longitudinal single-cell study of glucagon-like peptide-2 curen successful nan patients pinch short bowel syndrome. JCI Insight. doi.org/10.1172/jci.insight.194497