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Oct 2, 2015 - Gastrointestinal Symptoms and Altered Intestinal Permeability. Induced by Combat Training Are Associated with Distinct. Metabotypic Chan...
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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

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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.

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Journal of Proteome Research

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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

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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