Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2023; 14(12): 1824-1838
Published online Dec 15, 2023. doi: 10.4239/wjd.v14.i12.1824
Depletion of gut microbiota facilitates fibroblast growth factor 21-mediated protection against acute pancreatitis in diabetic mice
Qi-Yan Sun, Xu-Ye Wang, Zu-Pin Huang, Jing Song, En-Dong Zheng, Fang-Hua Gong, Xiao-Wang Huang
Qi-Yan Sun, Xu-Ye Wang, Fang-Hua Gong, School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
Qi-Yan Sun, Zhejiang Medical Products Service Center, Hangzhou 310012, Zhejiang Province, China
Zu-Pin Huang, Jing Song, En-Dong Zheng, Fang-Hua Gong, Xiao-Wang Huang, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cangnan Hospital of Wenzhou Medical University, Wenzhou 325800, Zhejiang Province, China
Author contributions: Sun QY, Wang XY and Huang ZP contributed equally to this work; Gong FH and Huang XW conceived the experiments, analyzed the data; Sun QY, Wang XY, Huang ZP, Song J and Zheng ED performed experiments, coordinated the study and oversaw all experiments, revised the paper; all authors discussed the results and commented on the manuscript.
Supported by the 2022 Zhejiang Provincial Health Science and Technology Plan, No. 2022KY1216.
Institutional review board statement: This study did not involve human experimentation.
Institutional animal care and use committee statement: The study was reviewed and approved by the Ethics Committee of the Laboratory Animal of Wenzhou Medical University Institutional Review Board (Approval No.xmsq2023-0426).
Conflict-of-interest statement: The author declare that there is no conflict of interest regarding the publication of this manuscript.
Data sharing statement: No additional data are available.
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: Xiao-Wang Huang, MD, Chief Physician, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cangnan Hospital of Wenzhou Medical University, No. 2288 Yucang Road, Lingxi Town, Wenzhou 325800, Zhejiang Province, China. hxw7@163.com
Received: August 22, 2023
Peer-review started: August 22, 2023
First decision: September 18, 2023
Revised: September 28, 2023
Accepted: November 25, 2023
Article in press: November 25, 2023
Published online: December 15, 2023
ARTICLE HIGHLIGHTS
Research background

Fibroblast growth factor 21 (FGF21) plays a pivotal role in regulating glucose and lipid metabolism. Acute pancreatitis (AP) is a common inflammatory disease with clinical manifestations. Diabetes exacerbates intestinal permeability and intestinal inflammation, thus leading to the progression to AP. Our previous study indicated that FGF21 significantly attenuated susceptibility to AP in mice.

Research motivation

Yet, whether FGF21 similarly protects AP in diabetic mice remains unexplored.

Research objectives

Herein, we were intrigued to investigate the potential protective role of FGF21 against AP in diabetic mice.

Research methods

In the present study, a mouse model of AP was established in db/db diabetic mice through ceruletide injections. By comparing the differences in AP indicators between diabetic mouse group (db), ceruletide-induced AP model group (AP), FGF21 treatment group (FGF21), and FGF21 combined with an antibiotic (Abx) cocktail treatment group (FGF21 + Abx), we investigated the protective effect of recombinant FGF21 protein and investigated whether FGF21 plays its role in the treatment of diabetic mice with AP by modulating the gut microbiota.

Research results

FGF21 notably diminished the levels of serum amylase, inflammatory factors and the histological evidence of inflammation in the pancreas and the small intestine in diabetic mice with AP. FGF21 also significantly altered the composition of the gut microbiota, reestablishing the Bacteroidetes/Firmicutes ratio. Upon treatment with an Abx cocktail to deplete the gut microbiota, the FGF21 + Abx group showed superior protective effect. The gut microbiota composition across different groups was further characterized, and a differential expression analysis of gene functions was undertaken using the PICRUSt2 prediction method. These findings suggested that FGF21 could potentially confer therapeutic effects on diabetic mice with AP by modulating the sulfate reduction I pathway and the superpathway of n-acetylceramide degradation in the gut microbiota.

Research conclusions

This study reveals the potential of FGF21 in improving pancreatic and intestinal damage recovery, reducing blood glucose levels, and reshaping gut microbiota composition in diabetic mice with AP. Notably, the protective effects of FGF21 are augmented when combined with the Abx cocktail. These findings provide new insights into the prevention and treatment of diabetes complicated by AP.

Research perspectives

Further investigation is required to elucidate the specific mechanisms by which the gut microbiota affects the protective effects of FGF21 against AP in diabetic mice.