Subscriber access provided by Deakin University Library
Article
Gastrointestinal symptoms and altered intestinal permeability induced by combat-training are associated with distinct metabotypic changes Lee Cheng Phua, Clive H Wilder-Smith, Yee Min Tan, Theebarina Gopalakrishnan, Reuben K Wong, Xinhua Li, Mary E Kan, Jia Lu, Ali Keshavarzian, and Eric Chun Yong Chan J. Proteome Res., Just Accepted Manuscript • DOI: 10.1021/acs.jproteome.5b00603 • Publication Date (Web): 02 Oct 2015 Downloaded from http://pubs.acs.org on October 23, 2015
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of Proteome Research is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 30
Journal of Proteome Research
1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Gastrointestinal symptoms and altered intestinal permeability induced
by
combat-training
are
associated
with
distinct
metabotypic changes
Lee Cheng Phua1, Clive H. Wilder-Smith2,5,*, Yee Min Tan1, Theebarina Gopalakrishnan1, Reuben K. Wong2,*, Xinhua Li2, Mary E. Kan3, Jia Lu3, Ali Keshavarzian4 and Eric Chun Yong Chan1,* 1
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore
2
Division of Gastroenterology and Hepatology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
3
Combat Care Laboratory, DSO National Laboratories, Singapore
4
Department of Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA
5
Brain-Gut Research Group, Bern, Switzerland
*
Corresponding authors
Correspondence: 1. Eric Chun Yong Chan, Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore. Email:
[email protected]; Tel: +65 65166137; Fax: +65 67791554 2. Clive
H.
Wilder-Smith,
Brain-Gut
Research
Group,
Gastroenterology
Group
Practice,
Bubenbergplatz 11, CH-3011 Bern, Switzerland. Email:
[email protected]; Tel: +41 31 312 3737; Fax: +41 31 312 3770 3. Reuben K. Wong, Division of Gastroenterology and Hepatology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore. Email:
[email protected],
[email protected]; Tel: +65 6772 2002; Fax: +65 6772 4361
ACS Paragon Plus Environment
Journal of Proteome Research
Page 2 of 30
2 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
ABSTRACT Physical and psychological stress have been shown to modulate multiple aspects of gastrointestinal (GI) physiology but its molecular basis remains elusive. We therefore characterized the stress-induced metabolic phenotype (metabotype) in soldiers during highintensity combat-training and correlated the metabotype with changes in GI symptoms and permeability. In a prospective, longitudinal study, urinary metabotyping was conducted on 38 male healthy soldiers during combat-training and a rest period using gas chromatographymass spectrometry. The urinary metabotype during combat-training was clearly distinct from the rest period [partial least squares discriminant analysis (PLSDA) Q2=0.581], confirming the presence of a unique stress-induced metabotype. Differential metabolites related to combat stress were further uncovered, including elevated pyroglutamate and fructose, and reduced gut microbial metabolites, namely hippurate and m-hydroxyphenylacetate [p
