Microflora Disturbance during Progression of Glucose Intolerance and Effect of Sitagliptin: An Animal Study

Abstract

Background. Emerging evidences have shown a close interplay between obesity, diabetes, and intestinal flora disturbance. Dipeptidyl peptidase-4 inhibitor, exemplified by sitagliptin, is highly efficacious in treating type 2 diabetes (T2DM), yet little is known if sitagliptin exerts beneficial effects on microbiota associated with obesity and T2DM. We evaluated changes of gut microbiota following the induction of obesity and T2DM in a streptozotocin treated high fat/high carbohydrate fed (HF/HC-STZ) rat model and explored the effect of sitagliptin on gut microbiota for HF/HC-STZ rats. Methods. Sitagliptin was administered via oral gavage to diabetic rats. Fecal DNA extraction and 454 pyrosequencing based on analysis of 16S rRNA genes was utilized to determine the overall structure of microbiota in fecal DNA samples. Results. Results showed that, at the level of phylum, there was higher abundance of Firmicutes and Tenericutes and less abundance of Bacteroidetes in obese rats compared to their lean counterparts. At the level of genus, short-chain fatty acid- (SCFA-) producing bacteria, Blautia, Roseburia, and Clostridium, and probiotics Lactobacillus, Bifidobacterium, and so forth were identified significantly different from each other among conditions. Conclusion. Marked shifts of the gut microbiota structure were observed in the rats during development of glucose intolerance. Intestinal flora changed in the process of glucose intolerance, and treatment of sitagliptin moderately corrected the dysbiosis of microbiota in T2DM.

Lactobacillus acidophilus JCM 1132 Strain and Its Mutant with Different Bacteriocin-Producing Behaviour Have Various In Situ Effects on the Gut Microbiota of Healthy Mice

“…A similar gut microbiota structure has also been observed in patients with type 2 diabetes and metabolic syndrome [53]. The abundance of Tenericutes has been linked to obesity or type 2 diabetes-associated metabolic parameters [54,55]. Although the effects of reducing the F/B ratio did not appear to be directly related to the presence or absence of bacteriocin during gavage in our study, treatment with L. acidophilus JCM 1132 had a delayed reducing effect on the F/B ratio.…”

The DPP-4 inhibitor sitagliptin alters the gut microbiota and prevents neuronal damage of hippocampus in STZ induced type 2 diabetic rats

“…Similarly, some researches found that gut microbiota were substantially altered in STZ-induced type 2 diabetic rats [15,30].…”

“…However, Waget A et al [14] reported that sitagliptin could regulate glucose level by triggering the gut-brain axis other than local inhibition of intestinal DPP-4 activity. Furthermore, sitagliptin treatment substantially changed the structure of gut microbiota in STZ-induced type 2 diabetic rats [15]. Additionally, recent studies have shown that sitagliptin could improve cognitive function in type 2 diabetic patients with and without Alzheimer's disease [16] and in insulin-resistant rats [17].…”

Considering gut microbiota in treatment of type 2 diabetes mellitus

“…It has been found that Sitagliptin and Vildagliptin, DPP-4 inhibitors, altered gut microbial composition in diabetic rats. 58,59 These drugs reduced the diversity of microbiota, increased the abundances of SCFA-producing bacteria including Blautia, Roseburia, Clostridium, Baceroides, and Erysipelotrichaeae in gut microbiota and corrected the Bacteroidetes/Firmicutes ratio. 58,59 Therefore, it has been suggested that these drugs may have beneficial effects on blood glucose partly through maintaining the gut barrier integrity and correcting the dysbiosis of intestinal microbiota in diabetes, although human studies are needed in this regard.…”