The gut microbiota plays a critical role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Increased fructose consumption and inadequate copper intake are two critical risk factors in the development of NAFLD. To gain insight into the role of gut microbiota, fecal metabolites, obtained from rats exposed to different dietary levels of copper with and without high fructose intake for 4 weeks, were analyzed by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC × GC-TOF MS). In parallel, liver tissues were assessed by histology and triglyceride assay. Our data showed that high fructose feeding led to obvious hepatic steatosis in both marginal copper deficient rats and copper supplementation rats. Among the 38 metabolites detected with significant abundance alteration between groups, short chain fatty acids were markedly decreased with excessive fructose intake irrespective of copper levels. C15:0 and C17:0 long chain fatty acids, produced only by bacteria, were increased by either high copper level or high fructose intake. In addition, increased fecal urea and malic acid paralleled the increased hepatic fat accumulation. Collectively, GC × GC-TOF MS analysis of rat fecal samples revealed distinct fecal metabolome profiles associated with the dietary high fructose and copper level, with some metabolites possibly serving as potential noninvasive biomarkers of fructose induced-NAFLD.
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