Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2023; 29(33): 4991-5004
Published online Sep 7, 2023. doi: 10.3748/wjg.v29.i33.4991
Diabetes exacerbates inflammatory bowel disease in mice with diet-induced obesity
Kendra L Francis, Kimberly M Alonge, Maria Cristina Pacheco, Shannon J Hu, Cody A Krutzsch, Gregory J Morton, Michael W Schwartz, Jarrad M Scarlett
Kendra L Francis, Jarrad M Scarlett, Department of Pediatric Gastroenterology and Hepatology, Seattle Children’s Hospital, Seattle, WA 98105, United States
Kendra L Francis, Kimberly M Alonge, Shannon J Hu, Cody A Krutzsch, Gregory J Morton, Michael W Schwartz, Jarrad M Scarlett, Diabetes Institute, University of Washington, Seattle, WA 98109, United States
Kimberly M Alonge, Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, United States
Maria Cristina Pacheco, Department of Laboratory Medicine and Pathology, Seattle Children's Hospital, Seattle, WA 98105, United States
Author contributions: Francis KL, Schwartz MW, and Scarlett JM conceived the study; Francis KL and Scarlett JM carried out the experiments and were responsible for the data collection, analysis, and interpretation; Hu SJ and Krutzsch CA participated in the data collection and image analysis; Pacheco MC was responsible for the pathologic analysis of tissues; Francis KL, Scarlett JM, Schwartz MW, Alonge KM, Pacheco MC, Morton GJ, Hu SJ, and Krutzsch CA participated in the study design and data interpretation; Francis KL was responsible for drafting the article; Morton GJ, Alonge KM, Schwartz MW, Pacheco MC, Scarlett SJ, Krutzsch CA, and Scarlett JM were responsible for revising and editing the manuscript.
Supported by The National Institutes of Health under the National Institute of Diabetes and Digestive and Kidney Diseases (NIH-NIDDK), No. DK114474 (JMS) and No. DK128383 (JMS), No. DK131695 (KLF), No. DK101997 (MWS), No. DK083042 (MWS), No. DK089056 (GJM) and No. DK124238 (GJM); Department of Defense (JMS), No. W81XWH2110635; The University of Washington Royalty Research Fund (JMS), No. A139339; The NIH-NIDDK T32 Training Grant (KLF), No. DK007742; The NIH-National Heart, Lung, and Blood Institute T32 Training Grant (KMA), No. HL007028; The NIH-NIDDK–funded Diabetes Research Center, No. P30DK017047; and The Nutrition Obesity Research Center at the University of Washington, No. P30DK035816.
Institutional review board statement: This study was exempted by the Ethics Committee of the University of Washington due to its not involving human subject research.
Institutional animal care and use committee statement: The experimental work involving animals conformed to the Guide for the Care and Use of Laboratory Animals. All procedures were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee at the University of Washington.
Conflict-of-interest statement: All authors have no conflicts of interest to declare.
Data sharing statement: There are no additional data available; all data are presented within the article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Jarrad M Scarlett, MD, PhD, Assistant Professor, Department of Pediatric Gastroenterology and Hepatology, Seattle Children’s Hospital, 750 East Republican Street F770, Seattle, WA 98195, United States. jarrad.scarlett@seattlechildrens.org
Received: June 14, 2023
Peer-review started: June 14, 2023
First decision: July 7, 2023
Revised: July 22, 2023
Accepted: August 21, 2023
Article in press: August 21, 2023
Published online: September 7, 2023
Processing time: 78 Days and 9.6 Hours
Core Tip

Core Tip: Metabolic syndrome affects many patients with inflammatory bowel disease (IBD). This study used mouse models of colitis to investigate how diabetes and obesity interact to impair intestinal barrier function and exacerbate IBD outcomes, highlighting the deleterious impact of sustained hyperglycemia on intestinal barrier integrity. We showed that diabetic hyperglycemia impairs the colonic mucin barrier and tight junction protein abundance in the setting of diet-induced obesity, which corresponds to worse clinical and histopathological IBD outcomes. These findings are important because as more patients with IBD are affected by obesity and/or diabetes, it is imperative to understand how these disease processes interact.