DIETARY RESISTANT STARCH ALTERS GUT MICROBIOTA, INTESTINAL CLAUDIN-7 EXPRESSION AND ALBUMINURIA IN DIABETIC MICE

M Snelson M1, De Pasquale C1, Tan S1, Coughlan M1 

1Department of Diabetes, Monash University, Mlebourne, Australia 

Aim: To investigate the gut targeting mechanisms by which resistant starch (RS) supplementation may be protective against diabetic nephropathy. 

Background: Dietary RS may be nephro-protective in diabetes, however whether this occurs via modulation of the gut microbiota and intestinal homeostasis have not been explored.  

Methods: Six week old non-diabetic mice (db/h), diabetic mice (db/db) and db/db mice on a regular chow diet supplemented with 25% RS (dbdb+RS) were maintained for ten weeks. 24-hour urine was collected for albumin measurement by ELISA. Ileum and jejunum sections were collected, RNA extracted, and cDNA synthesised for quantitative gene expression analysis. Cecal digesta were collected for microbiota analysis by 16S rRNA gene sequencing. 

Results: Diabetes was associated with an increase in albuminuria (23.4±14.4 vs 381.2±274.0µg/24h, P<0.001, dbh vs dbdb), which was reduced in diabetic mice receiving RS supplementation (381.2±274.0 vs 136.7±130.0µg/24h, P<0.01, dbdb vs dbdb+RS). Db/db mice had a reduction in relative expression of the tight junction expression Claudin-7 in both the jejunum and ileum (1.17±0.63 vs 0.22±0.13, P<0.01 and 1.19±0.61 vs 0.63±0.35, P<0.05, respectively, dbh vs dbdb) which was ameliorated with RS supplementation (0.22±0.13 vs 1.12±0.89, P<0.05 and 0.63±0.35 vs 1.22±0.50, P<0.05, respectively, dbdb vs dbdb+RS). Between db/db mice, RS favourably altered the microbiome, specifically an expansion of Verrucomicrobia, driven largely by the genus Akkermansia, and a contraction in Proteobacteria, driven by the sulphate reducing bacterial family Desulfovibrionaceae. 

Conclusions: These studies support the notion that dietary RS may be protective against renal disease via alteration of the gut microbiota and consequently intestinal homeostasis. 


Biography:  

Dr Matthew Snelson is a dietitian and researcher interested in the role of diet in altering disease states via modulation of the gut microbiota. He completed his PhD at Monash University in 2019, investigating the effects of a processed diet on gut homeostasis and the contribution that these changes make to the development of diabetic kidney disease. He is currently a Research Fellow in the Department of Diabetes, Monash University investigating the role of resistant starch on the development of diabetic nephropathy. 

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