Effects of Exogenous Dietary Advanced Glycation End Products on the Cross-Talk Mechanisms Linking Microbiota to Metabolic Inflammation

Abstract

Heat-processed diets contain high amounts of advanced glycation end products (AGEs). Here we explore the impact of an AGE-enriched diet on markers of metabolic and inflammatory disorders as well as on gut microbiota composition and plasma proteins glycosylation pattern. C57BL/6 mice were allocated into control diet (CD, n = 15) and AGE-enriched diet (AGE-D, n = 15) for 22 weeks. AGE-D was prepared replacing casein by methylglyoxal hydroimidazolone-modified casein. AGE-D evoked increased insulin and a significant reduction of GIP/GLP-1 incretins and ghrelin plasma levels, altered glucose tolerance, and impaired insulin signaling transduction in the skeletal muscle. Moreover, AGE-D modified the systemic glycosylation profile, as analyzed by lectin microarray, and increased Nε-carboxymethyllysine immunoreactivity and AGEs receptor levels in ileum and submandibular glands. These effects were associated to increased systemic levels of cytokines and impaired gut microbial composition and homeostasis. Significant correlations were recorded between changes in bacterial population and in incretins and inflammatory markers levels. Overall, our data indicates that chronic exposure to dietary AGEs lead to a significant unbalance in incretins axis, markers of metabolic inflammation, and a reshape of both the intestinal microbiota and plasma protein glycosylation profile, suggesting intriguing pathological mechanisms underlying AGEs-induced metabolic derangements.

Dysbiosis-Related Advanced Glycation Endproducts and Trimethylamine N-Oxide in Chronic Kidney Disease

“…Mastrocola et al explored the impact of an AGEs-enriched diet on inflammation, as well as on the composition of gut microbiota in mice. In an AGEs-rich diet group, N ε -CML deposition and the upregulation of RAGE were observed in the ileum portion of the intestine and submandibular salivary glands, with an increase in systemic inflammation assessed by the levels of IL-1β, IL-17, and TNF-α [ 124 ]. Using fecal microbiota analysis, they found that high AGEs exposure in the intestine affected the gut microbiota population, characterized by the reduction of Anaerostipes , one of the butyrate-producing species [ 124 ].…”

“…In an AGEs-rich diet group, N ε -CML deposition and the upregulation of RAGE were observed in the ileum portion of the intestine and submandibular salivary glands, with an increase in systemic inflammation assessed by the levels of IL-1β, IL-17, and TNF-α [ 124 ]. Using fecal microbiota analysis, they found that high AGEs exposure in the intestine affected the gut microbiota population, characterized by the reduction of Anaerostipes , one of the butyrate-producing species [ 124 ]. Another investigation has demonstrated that a high-AGEs diet reduces the levels of saccharolytic bacteria such as Ruminococcaceae and Alloprevotella , which are related to SCFAs’ production.…”

Effect of Advanced Glycation End-Products and Excessive Calorie Intake on Diet-Induced Chronic Low-Grade Inflammation Biomarkers in Murine Models

“…No change (→) (mRNA) [37] Liver No change (→) (mRNA) [38] [37] Plasma Control:10 pg/mL Affected: 20 pg/mL (↑) (Protein) [37] Control: 15 pg/mL Affected: 9 pg/mL (↓) (Protein) [39] Pro and antiinflammatory Adipokine Adiponectin Plasma Control: 90 µg/mL Affected: 60 µg/mL (↓) (Protein) [40] Control: 30 µg/mL Affected: 45 µg/mL (↑) (Protein) [41] Control: 8 ng/mL (→) (Protein) [37] Cytokine Interleukin 6 (IL-6)…”

“…[45] 18-fold change (↑) (mRNA) Plasma 3-fold change (↑) (mRNA) [46] Control: 4 pg/mL Affected: 2 pg/mL (↓) (Protein) [39] No change (→) (mRNA) [39] Table 1. Cont.…”

“…Tendency) Liver Control: 20 pg/mL Affected: 180 pg/mL (↑) (Protein) [52] Plasma Control: 900 pg/mL Affected: 1500 pg/mL (↑) (Protein) [52] Cluster of differentiation CD68 Clone ED1 (ED1) 2-fold change (↑) (mRNA) [37] Plasma Control: 1 pg/mL Affected: 5 pg/mL (↑) (Protein) [39] 2-fold change (↑) (mRNA) [46] Interleukin 16 (IL-16) Plasma 3.5-fold change (↑) (Protein) [48] No change (→) (Protein) [37] Interleukin 17 (IL-17) Plasma Control: 11 pg/mL Affected: 18 pg/mL (↑) (Protein) [39] Tumor necrosis factor alpha (TNF-α)…”