Regionally distinct alterations in the composition of the gut microbiota in rats with streptozotocin-induced diabetes

PLoS One. 2014 Dec 3;9(12):e110440. doi: 10.1371/journal.pone.0110440. eCollection 2014.


The aim of this study was to map the microbiota distribution along the gut and establish whether colon/faecal samples from diabetic rats adequately reflect the diabetic alterations in the microbiome. Streptozotocin-treated rats were used to model type 1 diabetes mellitus (T1D). Segments of the duodenum, ileum and colon were dissected, and the microbiome of the lumen material was analysed by using next-generation DNA sequencing, from phylum to genus level. The intestinal luminal contents were compared between diabetic, insulin-treated diabetic and healthy control rats. No significant differences in bacterial composition were found in the luminal contents from the duodenum of the experimental animal groups, whereas distinct patterns were seen in the ileum and colon, depending on the history of the luminal samples. Ileal samples from diabetic rats exhibited particularly striking alterations, while the richness and diversity obscured some of the modifications in the colon. Characteristic rearrangements in microbiome composition and diversity were detected after insulin treatment, though the normal gut flora was not restored. The Proteobacteria displayed more pronounced shifts than those of the predominant phyla (Firmicutes and Bacteroidetes) in the rat model of T1D. Diabetes and insulin replacement affect the composition of the gut microbiota in different, gut region-specific manners. The luminal samples from the ileum appear more suitable for diagnostic purposes than the colon/faeces. The Proteobacteria should be at the focus of diagnosis and potential therapy. Klebsiella are recommended as biomarkers of T1D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / classification*
  • Bacteria / isolation & purification*
  • Colon / microbiology*
  • DNA, Bacterial / analysis
  • Diabetes Mellitus, Experimental / microbiology*
  • Feces / microbiology*
  • High-Throughput Nucleotide Sequencing
  • Ileum / microbiology*
  • Klebsiella / classification
  • Klebsiella / isolation & purification
  • Male
  • Microbiota
  • Proteobacteria / classification
  • Proteobacteria / isolation & purification
  • Rats
  • Rats, Wistar
  • Sequence Analysis, DNA
  • Streptozocin


  • DNA, Bacterial
  • Streptozocin

Associated data

  • SRA/SRX642704

Grant support

Funding from TÁMOP-4.2.2/B-10/1-2010-0012 and GOP-1.1.1-11-2012-0128 grants is gratefully acknowledged. N.B. was supported by the Hungarian Scientific Research Fund, OTKA grant PD 108309 and by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TÁMOP 4.2.4.A/2-11-1-2012-0001 ‘National Excellence Program’. M.B. was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.