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Sumei Sha,1 Bin Xu,2 Chenyang Qiao,1 Kairuo Wang,1 Le Liu,3 Jie Wu,4 Wenqi Ma,5 Ameng Shi,5 Xin Liu1 1Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Radiotherapy, Tangdu Hospital of the Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Radiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Pathology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 5Department of Ultrasound, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Xin Liu, Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710004, People’s Republic of China, Email docliuxin126@xjtu.edu.cnBackground: Guselkumab, a monoclonal antibody targeting the p19 subunit of interleukin‑23 (IL‑23), is a treatment option in inflammatory bowel disease (IBD). Evidence in young‑onset Crohn’s disease (CD) in the first‑line setting remains scarce.Objective: To describe short-term clinical, biochemical, endoscopic and imaging outcomes with first-line guselkumab combined with exclusive enteral nutrition (EEN) in biologic-naïve young adults with CD.Methods: We report a case series of three biologic‑naïve young adults with moderate‑to‑severe CD confirmed by clinical, endoscopic, and imaging criteria. All received guselkumab combined with exclusive enteral nutrition as initial therapy and were followed for up to 20 weeks. Outcomes were assessed across clinical, endoscopic, and cross‑sectional imaging (intestinal ultrasound, computed tomography enterography, or magnetic resonance enterography) domains. Safety was monitored throughout.Results: All three patients achieved a clinical response and clinical remission by week 4. C‑reactive protein, fecal calprotectin, and bowel wall thickness decreased markedly after therapy. Computed tomography enterography and intestinal ultrasound suggested marked transmural improvement in all cases. Endoscopic assessment demonstrated endoscopic improvement or remission in all three patients. Diets were gradually liberalized in all patients. Guselkumab was generally well tolerated. Two patients exhibited mild, asymptomatic elevations of liver transaminases prior to the second or third dose, which were managed successfully with hepatoprotective therapy while continuing guselkumab. No serious adverse events occurred during follow‑up up to 20 weeks.Conclusion: In this three-case real-world series from China, first‑line guselkumab plus EEN was associated with rapid short-term improvement across clinical, biochemical, endoscopic and imaging domains and was generally well tolerated. These observations are preliminary and hypothesis-generating and require confirmation in larger prospective cohorts.Keywords: guselkumab, crohn’s disease, exclusive enteral nutrition, young-onset, case series, IL 23