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.

中文翻译：

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基于 1H NMR 的粪便代谢组学揭示了 d-半乳糖诱导的衰老大鼠胃肠功能的变化

d-半乳糖（d -gal）被广泛用于诱导衰老。然而，长期注射d -gal是否会影响衰老大鼠的胃肠功能，以及如何影响，目前尚不清楚。在本研究中，我们研究了d -gal 对衰老大鼠胃肠功能的影响，特别是从粪便代谢组学的角度。进行了生化和行为分析。此外，建立并应用了基于¹ H NMR 的代谢组学方法，并结合了多变量数据分析，包括主成分分析 (PCA) 和正交偏最小二乘判别分析 (OPLS-DA)。关于胃肠功能，d-gal 显着降低小肠推进率并延长胃肠道转运时间。此外，d -gal 显着增加氧化损伤。PCA 结果表明，d -gal 中断了衰老大鼠内源性小分子的代谢谱。此外，OPLS-DA 显示筛选并鉴定出 40 种代谢物与衰老大鼠胃肠功能的破坏有关。因此，七种代谢途径被认为是与d诱导的衰老大鼠胃肠功能相关的影响最大的途径。-gal，包括氨基酸代谢、能量代谢、肠道菌群代谢和短链脂肪酸代谢。首次从粪便代谢组学角度研究d -gal对老年大鼠胃肠功能的影响及其机制。目前的研究结果有利于进一步全面了解d -gal诱导的衰老，并将扩大d -gal在药理研究中的应用。