Xu CY, Zheng ZH, Yang K, Wu RR, Cao JQ, Duan JY. Distal small bowel resection with preservation of the terminal ileum suppresses hepatic gluconeogenesis via the Prevotellaceae_NK3B31_group-mediated 7-KLCA-FXR axis. World J Gastroenterol 2025; 31(43): 112483 [DOI: 10.3748/wjg.v31.i43.112483]
Corresponding Author of This Article
Jin-Yuan Duan, PhD, Associate Chief Physician, Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1519 Dongyue Avenue, Nanchang 330000, Jiangxi Province, China. duanjy2022@outlook.com
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Gastroenterology & Hepatology
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Basic Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Nov 21, 2025 (publication date) through Nov 20, 2025
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World Journal of Gastroenterology
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1007-9327
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Xu CY, Zheng ZH, Yang K, Wu RR, Cao JQ, Duan JY. Distal small bowel resection with preservation of the terminal ileum suppresses hepatic gluconeogenesis via the Prevotellaceae_NK3B31_group-mediated 7-KLCA-FXR axis. World J Gastroenterol 2025; 31(43): 112483 [DOI: 10.3748/wjg.v31.i43.112483]
World J Gastroenterol. Nov 21, 2025; 31(43): 112483 Published online Nov 21, 2025. doi: 10.3748/wjg.v31.i43.112483
Distal small bowel resection with preservation of the terminal ileum suppresses hepatic gluconeogenesis via the Prevotellaceae_NK3B31_group-mediated 7-KLCA-FXR axis
Chi-Ying Xu, Kun Yang, Ren-Ran Wu, Jin-Yuan Duan, Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, Jiangxi Province, China
Zhi-Hua Zheng, Jia-Qing Cao, Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, Jiangxi Province, China
Co-first authors: Chi-Ying Xu and Zhi-Hua Zheng.
Author contributions: Xu CY and Zheng ZH are co-first authors who have made significant contributions to this article; Xu CY, Zheng ZH, Cao JQ and Duan JY contributed to the conception of the study; Xu CY, Zheng ZH, Yang K and Wu RR performed the experiment; Cao JQ and Duan JY helped perform the analysis with constructive discussions; Xu CY, Zheng ZH, Cao JQ and Duan JY performed the data analyses and wrote the manuscript; all correspondence should be directed to Duan JY. All authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 82360168 and No. 81960154; Natural Science Foundation of Jiangxi Province, No. 20212BAB206020; and the Foundation of Health Commission of Jiangxi Province, No. 202310024.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Affiliated Hospital of Nanchang University.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at duanjy2022@outlook.com.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jin-Yuan Duan, PhD, Associate Chief Physician, Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1519 Dongyue Avenue, Nanchang 330000, Jiangxi Province, China. duanjy2022@outlook.com
Received: July 29, 2025 Revised: September 2, 2025 Accepted: October 13, 2025 Published online: November 21, 2025 Processing time: 115 Days and 1.1 Hours
Abstract
BACKGROUND
Distal small bowel resection with preservation of the terminal ileum (DBRPI) significantly improves glucose metabolism in rats.
AIM
To explore the underlying mechanisms of DBRPI in improving glucose metabolism.
METHODS
Following 8 weeks of a high-fat diet, the rats were randomly divided into the DBRPI group and the sham operation group. After surgery, body weight and glucose tolerance were monitored. At 6 weeks post-surgery, the composition of intestinal microbiota, bile acid levels, and the expression of farnesoid X receptor (FXR), Takeda G protein-coupled receptor 5, and glucagon-like peptide-1 (GLP-1) in the ileum were examined. Additionally, the gene expression of key enzymes involved in gluconeogenesis in the liver was evaluated.
RESULTS
DBRPI reduced body weight and improved glucose tolerance. At 6 weeks post-surgery, the abundance of Prevotellaceae_NK3B31_group and the level of 7-ketolithocholic acid (7-KLCA) were significantly increased, while the abundance of Desulfovibrio fairfieldensis and the level of α-muricholic acid were significantly decreased. The expression of FXR and GLP-1 in the terminal ileum was significantly upregulated. Furthermore, the expression of key gluconeogenic enzyme genes, glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1), was significantly downregulated. Correlation analysis showed that the Prevotellaceae_NK3B31_group was positively correlated with 7-KLCA and FXR, and negatively correlated with glucose tolerance, α-muricholic acid, G6PC, and PCK1.
CONCLUSION
DBRPI inhibits hepatic gluconeogenesis and improves glucose metabolism. The mechanism may be related to activation of the 7-KLCA-FXR signaling pathway mediated by the Prevotellaceae_NK3B31_group.
Core Tip: Distal small bowel resection with preservation of the terminal ileum (DBRPI) improves glucose tolerance and reduces weight in high-fat diet-fed rats. This effect is linked to altered gut microbiota and bile acids: Increased Prevotellaceae_NK3B31_group and 7-ketolithocholic acid (7-KLCA), alongside decreased Desulfovibrio fairfieldensis and α-muricholic acid. DBRPI upregulates ileal farnesoid X receptor (FXR) and glucagon-like peptide-1 (GLP-1) expression, and downregulates hepatic gluconeogenic genes. Critically, Prevotellaceae_NK3B31_group correlates positively with 7-KLCA and FXR, and negatively with glucose intolerance and gluconeogenesis. Thus, DBRPI likely improves glucose metabolism by activating the Prevotellaceae-mediated 7-KLCA-FXR pathway, enhancing GLP-1, and suppressing hepatic glucose production.
