1H NMR-Based Fecal Metabolomics Reveals Changes in Gastrointestinal Function of Aging Rats Induced by d-Galactose.

Abstract

d-galactose (d-gal) is widely used to induce aging. However, it is still unclear whether long-term injection of d-gal affects the gastrointestinal functions of aging rats, and how. In this study, we investigated the effects of d-gal on the gastrointestinal functions of aging rats, especially from the perspective of fecal metabolomics. Biochemical and behavioral analyses were performed. Besides, a ¹H NMR-based metabolomics approach was built and applied in combination with multivariate data analysis including principal components analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA). Regarding gastrointestinal functions, d-gal significantly decreased the small intestine propulsion rates and prolonged gastrointestinal transit time. In addition, d-gal significantly increased the oxidative damages. PCA results showed that d-gal interrupted the metabolic profiles of endogenous small molecules in aging rats. Furthermore, OPLS-DA showed that 40 metabolites were screened and identified to be involved in the disruption of gastrointestinal functions in aging rats. Accordingly, seven metabolic pathways were recognized as the most influenced pathways associated with gastrointestinal functions of aging rats induced by d-gal, including amino acid metabolism, energy metabolism, intestinal flora metabolism, and metabolism of short chain fatty acids. It is the first report to investigate the effects and underlying mechanisms of d-gal on gastrointestinal functions of aging rats from the perspective of fecal metabolomics. The current results are conducive to further comprehensively understand d-gal-induced aging and will expand the applications of d-gal in pharmacological researches.