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Thermally processed diet-induced albuminuria, Enterobacteriaceae expansion and cecal metabolome alterations are attenuated by resistant starch in diabetes
* , , , , , ,
1  Department of Diabetes, Central Clinical School, Monash University

Abstract:

Background:

Modern, processed diets are replete in dietary advanced glycation endproducts (AGEs) which contribute to chronic renal injury. This study investigated whether excess consumption of dietary AGEs alters gut ecology and exacerbates renal injury in diabetic mice, and if this could be ameliorated with resistant starch (RS) supplementation.

Methods:

Six-week-old diabetic mice (db/db) and non-diabetic mice (db/m) were randomised to receive a low AGE (LAGE, unbaked rodent chow) or a high AGE diet (HAGE, baked at 160°C for 1h), with or without 12.5% RS for 10 weeks. 24-hour urine was collected for the assessment of albuminuria. Intestinal permeability was assessed in vivo by the clearance of FITC-labelled dextran. Cecal digesta were collected for an untargeted metabolomics screen and microbiota analysis by 16S rRNA gene sequencing.

Results:

HAGE diet exacerbated albuminuria in diabetic mice which RS attenuated. The HAGE diet increased gut permeability of db/db mice, an effect not observed in HAGE+RS-fed db/db mice. In db/db mice, a HAGE diet was associated with an increase in Enterobacteriaceae, which was ameliorated by supplementation with RS. High-AGE-fed db/db mice had a unique cecal metabolome with a marked increase in metabolites from the phenylalanine, tryptophan and tyrosine pathways.

Conclusions:

HAGE-feeding increased intestinal permeability and Enterobacteriaceae, altered the cecal metabolome and worsened albuminuria in db/db mice. RS protected against HAGE-induced albuminuria and reversed changes observed in the microbiome and cecal metabolome. This study supports the notion that dietary AGEs contribute to DKD via alterations in gut homeostasis and indicate a potential renoprotective role for RS.

Keywords: advanced glycation endproducts; heat-treated diets; resistant starch; diabetic kidney disease; Enterobacteriaceae
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