Implication of the gut microbiome composition of type 2 diabetic patients from northern China

Abstract

Emerging evidence has suggested the association of the gut microbiome with some human diseases, including type 2 diabetes (T2D). In this study, we analyzed the gut microbiota from a cohort of healthy and diabetic Chinese individuals from Northern China. Pyrosequencing of the V4V5 region of 16S rRNA genes revealed a significant decrease in the gut microbiota diversity of diabetic patients as compared to healthy individuals. Butyrate-producing bacteria such as Bifidobacterium and Akkermansia were significantly decreased in diabetic patients. Furthermore, the abundance of Dorea was significantly increased in T2D individuals and negatively correlated with the abundance of butyrate-producing bacteria. The increase of Dorea could play a role in the development of T2D and has been previously overlooked. Importantly, functional analysis of the gut microbiome revealed for the first time that increased levels of butyrate production via transferases and the degradation of several amino acids due to gut microbial metabolism have strong correlations with T2D in Northern China. Moreover, the potential of gut microbiota-based classifiers to identify individuals with a high risk for T2D has been demonstrated in this study. Taken together, our findings have revealed a previously unappreciated association of the gut microbiome with T2D and have also suggested that changes in gut microbiota may be used to identify individuals at high risk for T2D.

Figure 1

Difference in alpha diversity of the microbial communities between type 2 diabetes (T2D) and healthy individuals. (a) Phylogenetic diversity analysis between microbial genera. (b) Diversity analysis based on the Chao1 index revealing the decrease of microbial diversity in T2D. Boxes represent the interquartile ranges (IQRs) between the first and third quartiles, and the line inside the boxes represents the median; notches show the 95% confidence interval for the medians. P-values were < 0.01 for both phylogenetic diversity and Chao1 indices.

Figure 2

Bacterial taxonomic analysis of gut microbiota. (a) Boxplot showing the top 10 gut bacteria of taxonomic abundance in the two groups at the genus level. Red and blue boxes represent type 2 diabetes (T2D) and healthy controls, respectively. (b) Seven bacteria at the genus level that were differentially abundant between T2D patients and healthy controls, as tested by a two-sided White’s non-parametric t-test. FDR-adjusted p values are reported at the right of the image. Figure was produced using STAMP.

Figure 3

Interconnection of the type 2 diabetes (T2D) associated gut bacteria. A co-occurrence network deduced from 68 bacteria enriched in T2D subjects and controls. Nodes depict OTUs with their taxonomic assignment. The prefixed “k__,” “p__,” “c__,” “o__,” “f__,” and “g__” indicate OTUs only annotated to the level of kingdom, phylum, class, order, family or genus. Sizes of the nodes represent the relative abundance of the OTUs. Connecting lines represent Spearman’s rank correlation coefficient p > 0.6 (blue line) or <−0.6 (red line). The width of the connecting lines is proportional to the absolute value of the correlation coefficient.

Figure 4

Heatmap showing the relative abundances of the 50 most predictive OTUs according to T2D classification. The color of the spot corresponds to the log-transformed relative abundance of the OTU. The genus names of the OTUs are labeled on the right.

Figure 5

The area under the ROC curve (AUC) of gut-microbiota-based T2D classification. Random forest classifiers were used to separate T2D patients and healthy controls based on the OTU-level gut microbiome composition. The grey area between the two outside curves represents the 95% confidence interval (CI) shape.