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

d-galactose (d-gal) is widely used to induce aging. However, it is still unclear whether long-term injection ofd-gal affects the gastrointestinal functions of aging rats, and how. In this study, we investigated the effects ofd-gal on the gastrointestinal functions of aging rats, especially from the perspective of fecal metabolomics. Biochemical and behavioral analyses were performed. Besides, a(1)H 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 thatd-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 byd-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 ofd-gal on gastrointestinal functions of aging rats from the perspective of fecal metabolomics. The current results are conducive to further comprehensively understandd-gal-induced aging and will expand the applications ofd-gal in pharmacological researches.

Automated summary

This study investigated the effects of d-gal on the gastrointestinal functions of aging rats, revealing significant impacts on small intestine propulsion rates, gastrointestinal transit time, and oxidative damages. Metabolomics analysis identified 40 metabolites involved in disruption of gastrointestinal functions, associated with pathways like amino acid metabolism and energy metabolism. This research provides insight into the mechanisms underlying d-gal-induced aging in rats and expands its applications in pharmacological research.