Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2019; 25(43): 6465-6482
Published online Nov 21, 2019. doi: 10.3748/wjg.v25.i43.6465
Metabolic syndrome attenuates ulcerative colitis: Correlation with interleukin-10 and galectin-3 expression
Marina Jovanovic, Bojana Simovic Markovic, Nevena Gajovic, Milena Jurisevic, Aleksandar Djukic, Ivan Jovanovic, Nebojsa Arsenijevic, Aleksandra Lukic, Natasa Zdravkovic
Marina Jovanovic, Natasa Zdravkovic, Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
Bojana Simovic Markovic, Nevena Gajovic, Ivan Jovanovic, Nebojsa Arsenijevic, Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
Milena Jurisevic, Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
Aleksandar Djukic, Department of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
Aleksandra Lukic, Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
Author contributions: Jovanovic M, Jovanovic I, Djukic A and Zdravkovic N designed the study; Jovanovic M, Simovic Markovic B and Gajovic N performed the study; Jovanovic M, Simovic Markovic B and Gajovic N collected data; and Jovanovic I, Gajovic N and Jovanovic M analyzed data; Jovanovic M, Lukic A, Arsenijevic N and Jovanovic I wrote the paper; All authors discussed the results and implications and commented on the manuscript at all stages.
Institutional review board statement: The study was reviewed and approved by the Clinical Center of Kragujevac and Faculty of Medical Sciences, University of Kragujevac, Serbia Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There is no conflict of interest to be reported.
Data sharing statement: All data used to support the findings of this study are included within the article. Technical appendix, statistical code, and dataset available from the corresponding author at bojana.simovicmarkovic@medf.kg.ac.rs.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: 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/
Corresponding author: Bojana Simovic Markovic, MD, PhD, Research Assistant Professor, Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia. bojana.simovicmarkovic@medf.kg.ac.rs
Telephone: +381-34-306800 Fax: +381-34-306800
Received: July 25, 2019
Peer-review started: July 25, 2019
First decision: August 27, 2019
Revised: October 24, 2019
Accepted: November 7, 2019
Article in press: November 7, 2019
Published online: November 21, 2019
ARTICLE HIGHLIGHTS
Research background

Ulcerative colitis (UC) is a chronic disease associated with many other diseases such as rheumatoid arthritis, multiple sclerosis, lupus, psoriasis, hypothyroidism, and metabolic syndrome (MetS). Among these diseases, the MetS is the most common comorbidity. There is no evidence considering whether the comorbidity with MetS alters the course of the UC.

Research motivation

We hope to offer reliable evidence that MetS affects the outcome of the UC, given the increasingly common comorbidity.

Research objectives

Test the impact of the MetS on the severity of UC and the local and systemic immune response.

Research methods

A total of 89 patients with de novo confirmed UC were enrolled in this cross-sectional study, and they were further divided in two groups, according to ATP III criteria: group without MetS (no MetS) and group with MetS. Severity of UC was determined by histological and clinical scores, fecal and serum cytokines levels were determined using an enzyme-linked immunosorbent assay, while cellular makeup of colon infiltrations was determined by flow cytometry.

Research resultsWhen compared to UC patients without MetS, clinically and histologically milder disease with higher serum level of immunosuppressive cytokine interleukin- 10 (IL-10) and fecal content of Galectin-3 (Gal-3) was observed in subjects with UC and MetS. This was accompanied with predomination of IL-10 over pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin-6, and interleukin-17 (IL-17) in the sera as well as Gal-3 over TNF-α and IL-17 in feces of UC patients with MetS. Significantly lower systemic values of IL-17, higher values of IL-10 and Gal-3 values in feces were determined in MetS patients in especially same clinical, endoscopic and histopathological stage of UC as patients without MetS. In addition, UC + MetS patients had higher percentage of IL-10 producing and Gal-3 expressing innate and acquired immune cells in lamina propria of affected colon tissue.

Research conclusions

UC patients with MetS have clinically and histologically milder disease. Predominance of Gal-3 and IL-10 over pro-inflammatory mediators in patients with MetS may present a mechanism for limiting the inflammatory process and subsequent tissue damage in UC.

Research perspectives

Future studies are needed to investigate the exact mechanism underlying the protective effect of MetS in biology of UC. And it is necessary to determinate the influence of developmental stages of MetS on the severity of UC. Large sample size studies are also required to confirm the current findings.