Transglucosidase improves the gut microbiota profile of type 2 diabetes mellitus patients: a randomized double-blind, placebo-controlled study

Abstract

Background: Recently, the relationship between gut microbiota and obesity has been highlighted. The present randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy of transglucosidase (TGD) in modulating blood glucose levels and body weight gain in patients with type 2 diabetes mellitus (T2DM) and to clarify the underlying mechanism by analyzing the gut microbiota of T2DM patients.

Methods: This study included 60 patients who received placebo or TGD orally (300 or 900 mg/day) for 12 weeks, and blood and fecal samples were collected before and after 12 weeks. Comparisons of fecal bacterial communities were performed before and after the TGD treatment and were performed between T2DM patients and 10 healthy individuals, using the terminal-restriction fragment length polymorphism analysis.

Results: The Clostridium cluster IV and subcluster XIVa components were significantly decreased, whereas the Lactobacillales and Bifidobacterium populations significantly increased in the T2DM patients compared with the healthy individuals. By dendrogram analysis, most of the healthy individuals (6/10) and T2DM patients (45/60) were classified into cluster I, indicating no significant difference in fecal bacterial communities between the healthy individuals and the T2DM patients. In the placebo and TGD groups, the bacterial communities were generally similar before and after the treatment. However, after 12 weeks of TGD therapy, the Bacteroidetes-to-Firmicutes ratio in the TGD groups significantly increased and was significantly higher compared with that in the placebo group, indicating that TGD improved the growth of the fecal bacterial communities in the T2DM patients.

Conclusions: Therefore, TGD treatment decreased blood glucose levels and prevented body weight gain in the T2DM patients by inducing the production of oligosaccharides in the alimentary tract and modulating gut microbiota composition.

Trial registration: UMIN-CTR UMIN000010318.

Figure 1

Flow diagram of patients included.

Figure 2

The HbA1c levels and BMIs before and after the treatment. Open circle, placebo; open square, TGD300; open triangle, TGD900.

Figure 3

Gut microbes in the healthy individuals and T2DM patients. Significant decreases in Clostridium cluster IV and Clostridium subcluster XIVa components were observed in the T2DM patients compared with the healthy individuals. In contrast, the Lactobacillales and Bifidobacterium populations significantly increased in the T2DM patients.

Figure 4

Dendrogram of the fecal bacteria structure in the T2DM patients and healthy individuals. T-RFLP patterns by BslI digestions were analyzed using the software GeneMaths (Applied Maths, Belgium), and the Pearson similarity coefficient analysis and unweighted pair-group method with arithmetic means were used to establish the type of dendrogram. Open triangle, healthy volunteers; open square, T2DM patients before the placebo treatment; closed square, T2DM patients after the placebo treatment; open circle, T2DM patients before the treatment; closed circle, T2DM patients after the treatment.

Figure 5

Bacteroidetes-to-Firmicutes ratio before and after the TGD treatment in the T2DM patients. After the TGD therapy, the Bacteroidetes-to-Firmicutes ratio in both TGD groups significantly increased compared with that before the TGD treatment and was also significantly higher than that in the placebo group.