Copyright
©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children
Francois-Pierre Martin, Ming-Ming Su, Guo-Xiang Xie, Seu Ping Guiraud, Martin Kussmann, Jean-Philippe Godin, Wei Jia, Andreas Nydegger
Francois-Pierre Martin, Seu Ping Guiraud, Martin Kussmann, Nestlé Institute of Health Sciences, 1015 Lausanne, Switzerland
Ming-Ming Su, Guo-Xiang Xie, Wei Jia, University of Hawaii Cancer Center, Honolulu, HI 96813, United States
Ming-Ming Su, Metabo-Profile Biotechnology (Shanghai) Co., Ltd., Shanghai 203230, China
Martin Kussmann, The Liggins Institute, The University of Auckland, 1023 Auckland, New Zealand
Jean-Philippe Godin, Nestlé Research Center, 1000 Lausanne 26, Switzerland
Andreas Nydegger, Division of Pediatric Gastroenterology, University of Lausanne, 1011 Lausanne, Switzerland
Author contributions: Martin FP, Godin JP, Jia W and Nydegger a conceived and designed the experiments; Su MM, Xie GX and Jia W performed the metabonomics experiments; Martin FP and Guiraud SP analyzed the data; all the authors wrote the paper.
Supported by Swiss National Science Foundation, No. 32003B_135466.
Institutional review board statement: This clinical study was approved by the Ethical Committee of the University of Lausanne, Switzerland (protocol 69/10), and conducted in the Pediatric Gastroenterology outpatient clinic of the University Hospital of Lausanne, Switzerland.
Conflict-of-interest statement: FPM, SPG, JPG are employees of the Nestlé Group.
Data sharing statement: Data may be available upon request to Francois-Pierre Martin and Andreas Nydegger, subject in particular, to ethical and privacy considerations.
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/
Correspondence to: François-Pierre Martin, PhD, Nestle Institute of Health Sciences, 1015 Lausanne, Switzerland. francois-pierre.martin@rd.nestle.com
Telephone: +0041-21-6326161
Received: February 7, 2017
Peer-review started: February 10, 2017
First decision: March 3, 2017
Revised: March 29, 2017
Accepted: May 4, 2017
Article in press: May 4, 2017
Published online: May 28, 2017
AIM
To identify metabolic signatures in urine samples from healthy and inflammatory bowel disease (IBD) children.
METHODS
We applied liquid chromatography and gas chromatography coupled to targeted mass spectrometry (MS)-based metabolite profiling to identify and quantify bile acids and host-gut microbial metabolites in urine samples collected from 21 pediatric IBD patients monitored three times over one year (baseline, 6 and 12 mo), and 27 age- and gender-matched healthy children.
RESULTS
urinary metabolic profiles of IBD children differ significantly from healthy controls. Such metabolic differences encompass central energy metabolism, amino acids, bile acids and gut microbial metabolites. In particular, levels of pyroglutamic acid, glutamic acid, glycine and cysteine, were significantly higher in IBD children in the course of the study. This suggests that glutathione cannot be optimally synthesized and replenished. Whilst alterations of the enterohepatic circulation of bile acids in pediatric IBD patients is known, we show here that non-invasive urinary bile acid profiling can assess those altered hepatic and intestinal barrier dysfunctions.
CONCLUSION
The present study shows how non-invasive sampling of urine followed by targeted MS-based metabonomic analysis can elucidate and monitor the metabolic status of children with different GI health/disease status.
Core tip: Despite the limited number of subjects, the longitudinal experimental design with a healthy reference group reveals insights into childhood metabolic status in relation to growth and disease. Metabolite profiling of urine samples collected non-invasively enables identification and monitoring of biochemical signatures linked to metabolic and nutritional requirements in pediatric populations with inflammatory bowel disease (IBD). In the present study, a distinct biochemical process related to glutathione, glycine and bile acid metabolism distinguished children with IBD from healthy matched controls.
