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

• Published in: Microbiology (Society for General Microbiology) Vol. 161; no. Pt 1; pp. 182 - 193
• Main Authors: Patterson, Elaine, Marques, Tatiana M, O'Sullivan, Orla, Fitzgerald, Patrick, Fitzgerald, Gerald F, Cotter, Paul D, Dinan, Timothy G, Cryan, John F, Stanton, Catherine, Ross, R Paul
• Format: Journal Article
• Language: English
• Published: England 01.01.2015
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - adverse effects; Biodiversity; Diabetes Mellitus, Experimental - etiology; Diabetes Mellitus, Type 1 - etiology; Disease Models, Animal; Disease Progression; Fatty Acids, Volatile - metabolism; Intestines - microbiology; Lactic Acid - biosynthesis; Male; Metagenome; Microbiota; Rats; Rats, Sprague-Dawley; Streptozocin - administration & dosage; Streptozocin - adverse effects
• ISSN: 1350-0872; 1465-2080; 1465-2080
• DOI: 10.1099/mic.0.082610-0

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 STZ kg(-1)) of STZ, administered via the intraperitoneal cavity. Total DNA was isolated from faecal pellets at weeks 0 (pre-STZ injection), 1, 2 and 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 the microbiota was apparent post-STZ injection and for 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 separation 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.