Streptozotocin-induced type-1-diabetes disease onset in Sprague–Dawley rats is associated with an altered intestinal microbiota composition and decreased diversity

Elaine Patterson, Tatiana M Marques, Orla O'Sullivan, Patrick Fitzgerald, Gerald F Fitzgerald, Paul D Cotter, Timothy G Dinan, John F Cryan, Catherine Stanton, R Paul Ross

There is a growing appreciation that microbiota composition can significantly affect host health and play a role in disease onset and progression. This study assessed the impact of streptozotocin (STZ) induced type-1-diabetes (T1D) on intestinal microbiota composition and diversity in Sprague-Dawley rats, compared with healthy controls over time. T1D was induced by injection of a single dose (60 mg/Kg) of STZ, administered via the intraperitoneal cavity. Total DNA was isolated from faecal pellets at week 0 (pre- STZ injection), week 1, week 2, week 4 and from caecal content at week 5 from both healthy and T1D groups. High throughput 16S rRNA sequencing was employed to investigate intestinal microbiota composition. The data revealed that although intestinal microbiota composition between the groups was similar at week 0, a dramatic impact of T1D development on microbiota composition was apparent post- STZ injection and up to 5 weeks. Most notably, T1D onset was associated with a shift in the Bacteroidetes: Firmicutes ratio (P < 0.05), while at the genus level, increased proportions of lactic acid producing bacteria such as Lactobacillus and Bifidobacterium were associated with the later stages of T1D progression (P < 0.05). Coincidently, T1D increased caecal lactate levels (P < 0.05). Microbial diversity was also reduced following T1D (P < 0.05). Principle co-ordinate analyses demonstrated temporal clustering in T1D and control groups with distinct separations between groups. The results provide a comprehensive account of how T1D is associated with an altered intestinal microbiota composition and reduced microbial diversity over time.