Microbiome–Metabolomics Analysis of the Impacts of Long-Term Dietary Advanced-Glycation-End-Product Consumption on C57BL/6 Mouse Fecal Microbiota and Metabolites

Thermally processed diets are widely consumed, although advanced-glycation end products (AGEs) are unavoidably formed. AGEs, clusters of protein-cross-linking products, become less digestible because they impair intestinal peptidase proteolysis. We characterized the impacts of dietary AGEs on gut microbiota through a microbiome-to-metabolome association study. C57BL/6 mice were fed a heat-treated diet (high-AGE diet, H-AGE) or a standard AIN-93G diet (low-AGE diet, L-AGE) for 8 months. Fecal-microbiota composition was examined by 16S rDNA sequencing, and fecal-metabolome profile was evaluated by gas chromatography-tandem time-of-flight mass spectrometry (GC-TOF-MS). Reduced α-diversity and altered microbiota composition with elevated Helicobacter levels were found in the H-AGE group, and among the 57 perturbed metabolites, protein-fermentation products (i.e., p-cresol and putrescine) were increased. Major dysfunctional metabolic pathways were associated with carbohydrate and amino acid metabolism in two groups. Moreover, high correlations were found between fluctuant gut microbiota and metabolites. These findings might reveal the underlying mechanisms of the detrimental impacts of dietary AGEs on host health.