Abstract
Background: Although substantial efforts have been made to link the gut microbiota to type 2 diabetes, dynamic changes in the fecal microbiome under the pathological conditions of diabetes have not been investigated.Methods: Four male Zucker diabetic fatty (ZDF) rats received Purina 5008 chow [protein = 23.6%, Nitrogen-Free Extract (by difference) = 50.3%, fiber (crude) = 3.3%, ash = 6.1%, fat (ether extract) = 6.7%, and fat (acid hydrolysis) = 8.1%] for 8 weeks. A total of 32 stool samples were collected from weeks 8 to 15 in four rats. To decipher the microbial populations in these samples, we used a 16S rRNA gene sequencing approach.Results: Microbiome analysis showed that the changes in the fecal microbiome were associated with age and disease progression. In all the stages from 8 to 15 weeks, phyla Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria primarily dominated the fecal microbiome of the rats. Although Lactobacillus and Turicibacter were the predominant genera in 8- to 10-week-old rats, Bifidobacterium, Lactobacillus, Ruminococcus, and Allobaculum were the most abundant genera in 15-week-old rats. Of interest, compared to the earlier weeks, relatively greater diversity (at the genus level) was observed at 10 weeks of age. Although the microbiome of 12-week-old rats had the highest diversity, the diversity in 13–15-week-old rats was reduced. Spearman’s correlation analysis showed that F/B was negatively correlated with age. Random blood glucose was negatively correlated with Lactobacillus and Turicibacter but positively correlated with Ruminococcus and Allobaculum and Simpson’s diversity index.Conclusion: We demonstrated the time-dependent alterations of the abundance and diversity of the fecal microbiome during the progression of diabetes in ZDF rats. At the genus level, dynamic changes were observed. We believe that this work will enhance our understanding of fecal microbiome development in ZDF rats and help to further analyze the role of the microbiome in metabolic diseases. Furthermore, our work may also provide an effective strategy for the clinical treatment of diabetes through microbial intervention.
Highlights
Type 2 diabetes mellitus (T2DM) is currently the most prevalent metabolic disease in the world and is characterized by insulin resistance, with an initial increase in insulin secretion, but subsequent beta cell death and insulin insufficiency over time
The gut microbiota has increasingly been recognized as a key contributor to T2DM, and T2DM can be linked to dysbiosis of the intestinal microbiota (Cox et al, 2014; Forslund et al, 2015; Yano et al, 2015)
Two independent studies based on fecal samples from European and Chinese populations showed increased abundances of opportunistically pathogenic Clostridium species and decreased abundances of butyrate-producing Roseburia, Faecalibacterium, and Eubacterium species associated with T2DM patients (Qin et al, 2012; Karlsson et al, 2013)
Summary
Type 2 diabetes mellitus (T2DM) is currently the most prevalent metabolic disease in the world and is characterized by insulin resistance, with an initial increase in insulin secretion, but subsequent beta cell death and insulin insufficiency over time. Two independent studies based on fecal samples from European and Chinese populations showed increased abundances of opportunistically pathogenic Clostridium species and decreased abundances of butyrate-producing Roseburia, Faecalibacterium, and Eubacterium species associated with T2DM patients (Qin et al, 2012; Karlsson et al, 2013). Karlsson et al (2013) found that increased abundances of Lactobacillus gasseri and Streptococcus mutans can predict insulin resistance, while Qin et al (2012) found enrichment in Escherichia coli associated with current T2DM patients. Numerous studies have shown significant changes in the composition and diversity of the fecal microflora under conditions of diabetes. Substantial efforts have been made to link the gut microbiota to type 2 diabetes, dynamic changes in the fecal microbiome under the pathological conditions of diabetes have not been investigated
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