Background/Aims: Over-consumption of dietary AGEs, which are formed by heat-treatment of foodstuffs, is thought to lead to CKD. Research suggests that AGEs may modulate gut microbiota. The aim of this study was to characterise the effects of dietary AGEs on gut homeostasis and CKD.
Methods: Male C57BL/6 mice 6-8 weeks old were fed (ad libitum) a low AGE diet (unbaked rodent chow, LAGE) (n=10-20) or a high AGE diet (baked rodent chow, 160 degrees C for 1h, 5-fold higher AGE content, HAGE) (n=10-16) for 24 weeks. Urine albumin was measured by ELISA. Expression of the tight junction protein occludin was determined in jejenum by qPCR. Plasma endotoxin was measured using the Limulus Amebocyte Lysate assay. 16S rRNA sequencing of caecal extracts was used to profile the gut microbiome.
Results: Chronic consumption of dietary AGEs led to increased caecal bacterial diversity (LAGE vs HAGE, mean ± SEM, 0.86 ± 0.02 vs 0.95 ± 0, Simpson diversity index, p=0.0002) and decreased occludin expression in the jejunum (1.17 ± 0.23 vs 0.43 ± 0.08 fold change, p= 0.003). Plasma endotoxin was increased after high AGE feeding (1.45 ± 0.12 vs 1.91 ± 0.14 EU/ml, p=0.028). The HAGE diet increased urinary albumin excretion (36.04 ± 3.55 vs 59.61 ± 4.05 μg/24 hours, p=0.0003).
Conclusions: These data indicate that excess consumption of AGEs leads to albuminuria, which is associated with increased intestinal permeability and alterations in gut microbiome. This association remains to be fully defined. Further studies in this area are warranted.
Funding source: N/A