Plasma metabolomic profiles reveal regulatory effect of chitosan oligosaccharides on loperamide-induced constipation in mice.

ABSTRACT

Chitosan oligosaccharides (COS) can improve the symptoms of constipation. In this study, we further explored the regulator effect of COS on aberrant plasma metabolomics in constipated mice. Using untargeted metabolomic analysis by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS), we identified several most significantly changed metabolic pathways in plasma of constipated mice induced by loperamide, including those correlated with the metabolisms of sphingolipid, glycerophospholipid, tryptophan, bile acids, unsaturated fatty acids, and amino acids. The changes in these metabolic pathways were reversed by COS treatment largely. Furthermore, the mRNA levels of some key target genes related to the above metabolic pathways in colon samples were detected by reverse transcription-polymerase chain reaction analysis. We showed that COS significantly suppressed the abnormal expression of these genes, including ceramide glucosyltransferase (CGT), sphingolipid 4-desaturase (DEGS2), alkaline ceramidase (ACER1), sphingosine kinase 2 (SPHK2), lysophosphatidylcholine acyltransferase (LPCAT1), and aromatic-L-amino-acid (DDC). These data provide insight into the mechanisms by which COS ameliorates loperamide-induced constipation in mice.