Alterations of Gut Microbiota in Type 2 Diabetes Individuals and the Confounding Effect of Antidiabetic Agents

Abstract

Type 2 diabetes is a leading cause of morbidity and a common risk of several disorders. Identifying the microbial ecology changes is essential for disease prediction, therapy, and prevention. Thus, our study is aimed at investigating the intestinal microbiota among healthy and type 2 diabetes individuals and exploring the effect of antidiabetic agents on gut bacterial flora. 24 type 2 diabetes (metformin, glimepiride, and nontherapeutic subgroups; N = 8) and 24 healthy control subjects were enrolled in this study, and intestinal bacterial microbiota was investigated by analyzing V3-V4 regions of 16S rRNA gene sequence. Numerous alterations were observed in the gut microbial community of diabetic individuals. These changes were characterized by a significant lowered abundance of Faecalibacterium, Fusobacterium, Dialister, and Elusimicrobium in the nontherapeutic subgroup compared to the healthy control group. Likewise, correlation analysis showed a substantial decline in gut microbiota richness and diversity with the duration of illness. Furthermore, antidiabetic agents restored to some extent the richness and diversity of gut microbiota and improved the abundance of many beneficial bacteria with a significant increase of Methanobrevibacter in the metformin subcategory compared to the nontherapeutic subgroup. In return, they decreased the abundance of some opportunistic pathogens. The findings of this study have added a novel understanding about the pathogenesis of the disease and the mechanisms underlying antidiabetic therapy, which are of potential interest for therapeutic lines and further studies.

Figure 1

Multisample comparison analysis (beta diversity indices) between the type 2 diabetes mellitus (T2DM) group and healthy control (HC) individuals. PCoA based on (a) unweighted_unifrac, (b) NMDS Plot, and (c) unweighted beta diversity compared the microbial community of the type 2 diabetes group (n = 24) with healthy individuals (n = 24). (d) Anosim analysis describes the variation between and within the groups. R value is between -1 and 1. R value greater than zero indicates a significant difference between groups, while less than zero indicates that the difference within the group is greater than between the groups. The reliability of the statistical analysis is represented by probability value (P < 0.05 indicates that the statistic is significant). A: label of T2DM samples; B: label of HC samples; n: number.

Figure 2

Comparison of gut microflora between HC (n = 24) and T2DM (n = 24) individuals. (a) and (b) show the relative abundance of bacteria at the phylum and genus level, respectively. HC: healthy control; n: number; T2DM: type 2 diabetes mellitus.

Figure 3

The LEfSe analysis findings. (a) The most deferentially abundant taxa in HC (n = 24) and T2DM (n = 24) individuals have been analyzed using LEfSe (LDA effect size software). Linear discriminant analysis (LDA) scores reveal the statistically significant biomarkers between the groups (biomarker with LDA score greater than the set value, the default setting is 4). (b) The taxonomy of the most deferentially abundant taxa. HC: healthy control; n: number; T2DM: type 2 diabetes mellitus.

Figure 4

Correlation of alpha diversity indices with age (n = 48), BMI (n = 48), and diabetes duration (n = 24) of the study participants. BMI: body mass index; n: number; T2DM: type 2 diabetes mellitus.

Figure 5

Correlation of age (n = 48) and BMI (n = 48) of the study participants with the relative abundance gut flora at both (a) phylum and (b) genus levels. ∗P < 0.05 and ∗∗P < 0.01. BMI: body mass index; n: number.