Abstract

Phytosterols are known to reduce plasma cholesterol levels and thereby reduce cardiovascular risk. Studies conducted on human and animal models have demonstrated that these compounds have also anti-inflammatory effects. Recently, an experimental colitis model (dextran sulphate sodium-induced) has shown that pre-treatment with phytosterols decreases infiltration of inflammatory cells and accelerates mucosal healing. This study aims to understand the mechanism underlying the colitis by analysing the end-products of the metabolism in distal colon and liver excised from the same mice used in the previous work. In particular, an unsupervised gas chromatography-mass spectrometry (GC-MS) and NMR based metabolomics approach was employed to identify the metabolic pathways perturbed by the dextran sodium sulphate (DSS) insult (i.e. Krebs cycle, carbohydrate, amino acids, and nucleotide metabolism). Interestingly, phytosterols were able to restore the homeostatic equilibrium of the hepatic and colonic metabolome.

Highlights

  • Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions affecting the gastrointestinal tract[1]

  • The 40 mice employed in this study generated 4 groups: controls (CT), dextran sodium sulphate (DSS)-treated group (DS), phytosterols-treated group (PH), and the colitis phytosteroltreated group (PD)

  • Liver and distal colons were recovered from each animal and they were both analysed by gas chromatography-mass spectrometry (GC-mass spectrometry (MS)), while only the liver samples were further investigated by nuclear magnetic resonance (NMR)

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Summary

Introduction

Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions affecting the gastrointestinal tract[1]. IBD animal models are often chosen for their robustness and resemblance to human IBD regarding the disruption of the colonic epithelial layer and the progressive immune and inflammatory responses[9,10] In this frame, Aldini et al performed for the first time a longitudinal preventive and therapeutic study about the role of phytosterols in the prevention/induction and remission of inflammation in an experimental murine colitis model[11]. The results of such study showed that pre-treatment with phytosterols reduces the clinical symptoms and exerts a protective effect on the induced colonic inflammation, decreasing infiltration of inflammatory cells, and accelerating mucosal healing These effects have been related to the phytosterols antioxidant properties, suggesting that they may be taken in consideration as potential nutraceutical tool in the management (prevention/remission) of IBD and other intestinal inflammatory diseases

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