Integrative Metagenomic Analyses Reveal Gut Microbiota-Derived Multiple Hits Connected to Development of Diabetes Mellitus

Abstract

Background/objectives: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with gut dysbiosis. To investigate the association between gut microbiota and T2DM in a Saudi Arabian population.

Methods: We conducted a comparative analysis of fecal microbiota from 35 individuals, including both T2DM patients and healthy controls. 16S rRNA gene sequencing was employed to characterize the microbial community structure.

Results: Our findings revealed significant differences in microbial composition between the two groups. The T2DM group exhibited a higher abundance of Firmicutes and lower levels of Bacteroidetes compared to the healthy control group. At the genus level, T2DM patients showed a decrease in butyrate-producing bacteria such as Bacteroides and Akkermansia, while an increase in Ruminococcus and Prevotella was observed. Additionally, the T2DM group had a higher abundance of Faecalibacterium, Agathobacter, and Lachnospiraceae, along with a lower abundance of Bacteroides.

Conclusions: These results suggest that alterations in gut microbiota composition may contribute to the development of T2DM in the Saudi Arabian population. Further large-scale studies are needed to validate these findings and explore potential therapeutic interventions targeting the gut microbiome.

Keywords: 16S rRNA sequencing; T2DM; function of gut microbiota; gut microbiome; gut microbiota; gut microbiota dysbiosis; metabolic disorder; metagenomics; microbial composition; type 2 diabetes.

Figure 1

(A) Relative abundance of the top phyla in T2DM and healthy individuals. X-axis represents the diabetes samples in red and healthy samples in green. Y-axis represents relative abundance as a percentage. (B) Heatmap illustrating the distribution of top phyla across samples, with hierarchical clustering applied to both samples and phyla. Columns represent the sample while rows represent phyla.

Figure 2

(A) Venn diagram depicting shared and unique taxa between T2DM and healthy individuals. (B) Differential abundance analysis of specific genera between T2DM and healthy groups. The left panel presents the bar graphs depicting mean value of the abundance of the genus in each group. The right panel is the confidence interval of between-group variations. The right-most value is the p-value of the significance test of between-group variation using the t-test. (C–E) Comparative analysis of the relative abundance of top phyla, families, and genera between T2DM and healthy groups.

Figure 3

UPGMA clustering of samples based on weighted UniFrac distance, with the relative abundance of phyla visualized for each sample. The phylogenetic tree shows the distances between samples, with T2DM samples marked in red and healthy samples in blue. The accompanying bar chart displays the abundance of microbial taxa, highlighting the dominance of phyla.

Figure 4

Principal coordinate analysis (PCoA) plots based on weighted and unweighted UniFrac distances, illustrating the separation between T2DM and healthy samples. Each point on the plot represents a sample, positioned according to one principal component on the X-axis and another on the Y-axis. The points are color-coded by group. The percentage shown on each axis indicates the contribution of that principal component to the overall variance among the samples.

Figure 5

Box plots comparing the relative abundance of specific metabolic pathways between T2DM and healthy individuals: (A) glycogen synthesis pathway; (B) glycolysis pathway; and (C) anaerobic glycolysis pathway.

Figure 5

Box plots comparing the relative abundance of specific metabolic pathways between T2DM and healthy individuals: (A) glycogen synthesis pathway; (B) glycolysis pathway; and (C) anaerobic glycolysis pathway.