Long-term ingestion of β-lactoglobulin-bound AGEs induces colonic inflammation by modulating RAGE (TLR4)/MYD88/NF-κB signaling pathway and gut microbiota in mice

Abstract

Thermally processed foods are rich in advanced glycation end products (AGEs). Our study aimed to investigate the effects of long-term ingestion of β-lactoglobulin bound AGEs (β-LG AGEs) on the gut microenvironment and underlying mechanisms. BALB/c mice were orally administered with β-LG AGEs (60/120 mg/kg·bw) for 16 weeks. In this study, β-LG AGEs significantly induced oxidative stress and inflammation (TNF-α, IL-1β and IL-6), caused the lipid metabolism disorder, and led to the intestinal barrier dysfunction. Besides, the relative abundance of Lactobacillus, Odoribacter, and Parasutterella were increased by β-LG AGEs, which was positively correlated with the inflammation and epithelium barrier damage. Furthermore, β-LG AGEs were found to significantly decrease the content of short-chain fatty acids, such as acetic, propionic, butyric, and valeric acids, in feces, likely due to the impact of β-LG AGEs on the gut microbiota composition and structure. Additionally, β-LG AGEs were found to significantly downregulate the expression of colonic tight junction proteins, indicating their potential impact on intestinal barrier function. The potential molecular mechanism involved the RAGE/TLR4-mediated activation of NF-κB signaling pathway. These findings shed light on the harmful effects of food-borne β-LG AGEs on gut health.

Keywords

• Advanced glycation end products
• Gut microbiota
• Lipopolysaccharide
• Tight junction protein
• Short chain fatty acids
• The receptor of advanced glycation end products (Toll-like receptor 4)/myeloid differentiation factor 88/ nuclear factor kappa-B signal pathway