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Clinical Research and Public HealthIn-Press PreviewClinical ResearchGastroenterology Open Access | 10.1172/jci.insight.194497

Longitudinal single-cell analysis of glucagon-like peptide-2 treatment in the patients with short bowel syndrome

Yumi Kudo,1 Kentaro Miyamoto,2 Shohei Suzuki,2 Akihiko Chida,2 Anna Tojo,2 Mai Hasegawa,2 Arina Shigehara,2 Ikuko Koya,3 Yoshinari Ando,3 Masayasu Sato,1 Aya Kondo,1 Tomoko Kumagai,1 Harunori Deguchi,1 Yoshiki Sugiyama,1 Yoko Ito,1 Koji Shirosaki,1 Satoko Yamagishi,1 Yutaro Maeda,1 Hiroki Kanamori,1 Motohiro Kano,1 Mototoshi Kato,1 Hanako Tsujikawa,4 Yusuke Yoshimatsu,2 Kaoru Takabayashi,5 Koji Okabayashi,6 Takanori Kanai,2 Naoki Hosoe,5 Motohiko Kato,5 Jonathan Moody,3 Chung-Chau Hon,3 Tatsuo Kuroda,1 Yohei Yamada,1 Akihiro Fujino,1 and Tomohisa Sujino7

1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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1Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

2Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

3Laboratory for Regulatory Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

4Department of Pathology, Keio University School of Medicine, Tokyo, Japan

5Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

6Department of Surgery, Keio University School of Medicine, Tokyo, Japan

7Department of Multidimensional Analysis of Gastrointestinal Biology, Sakagu, Keio University School of Medicine, Tokyo, Japan

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Published August 7, 2025 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.194497.
Copyright © 2025, Kudo et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published August 7, 2025 - Version history
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Abstract

BACKGROUND. Glucagon-like peptide-2 (GLP-2) analogs are used clinically to enhance nutrient absorption in patients with short bowel syndrome (SBS); however, the precise mechanism remains unclear. To address this, the study aimed to clarify the dynamics of intestinal epithelial cells and immune cells in patients with SBS treated with GLP-2 analogs.

METHODS. Five male patients diagnosed with SBS, all of whom received treatment with the GLP-2 analog teduglutide, were included in the study. We conducted longitudinal single-cell RNA sequencing (scRNA-seq) analysis of intestinal tissue from SBS patients over a year, integrating microbiome composition analysis.

RESULTS. After treatment, the alpha diversity of the gut microbiome increased, indicating a more varied microbial environment. ScRNA-seq analysis revealed a reduction of T helper 2 cells and an increase in regulatory T (Treg) cells, suggesting a shift towards an immunoregulatory intestinal environment. Additionally, nutrient-absorbing enterocyte-Top2 and middle clusters expanded, enhancing the absorption capacity, whereas major histocompatibility complex class I/II-expressing enterocyte-Top1 cells declined, potentially modulating immune responses.

CONCLUSION. The study findings indicate that GLP-2 analogs reshape intestinal immunity and microbiota, fostering a less inflammatory environment while promoting nutrient uptake efficiency. 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.

FUNDING. This work was supported by Sakaguchi Memorial Foundation, Grants-in-Aid from the Japanese Society for the Promotion of Science (JSPS) (21K18272, 23H03665, 23H02899, 23K27590, 25K22627, 23K08037), JST FOREST(21457195), and the Takeda Japan Medical Office Funded Research Grant 2022.

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