Diabetes Metab J.  2021 Jan;45(1):77-85. 10.4093/dmj.2019.0202.

Metagenomic Analysis of the Gut Microbiome Reveals Enrichment of Menaquinones (Vitamin K2) Pathway in Diabetes Mellitus

• Dash NR
• Al Bataineh MT

• KMID: 2514076
• DOI: http://doi.org/10.4093/dmj.2019.0202

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with a high prevalence worldwide, especially among overweight and obese populations. T2DM is multifactorial with several genetic and acquired risk factors that lead to insulin resistance. Mounting evidence indicates that alteration of gut microbiome composition contribute to insulin resistance and inflammation. However, the precise link between T2DM and gut microbiome role and composition remains unknown.

We evaluated the metabolic capabilities of the gut microbiome of twelve T2DM and six healthy individuals through shotgun metagenomics using MiSeq platform.

We identified no significant differences in the overall taxonomic composition between healthy and T2DM subjects when controlling for differences in diet. However, results showed that T2DM enriched in metabolic pathways involved in menaquinone (vitamin K2) superpathway biosynthesis (PWY-5838) as compared to healthy individuals. Covariance analysis between the bacterial genera and metabolic pathways displaying difference in abundance (analysis of variance P<0.05) in T2DM as compared to healthy subjects revealed that genera belonging Firmicutes, Actinobacteria, and Bacteroidetes phyla contribute significantly to vitamin K2 biosynthesis. Further, the microbiome corresponding to T2DM with high glycosylated hemoglobin (HbA1c) (>6.5%) exhibit high abundance of genes involved in lysine biosynthesis and low abundance of genes involved in creatinine degradation as compared to T2DM with lower HbA1c (<6.5%).

The identified differences in metabolic capabilities provide important information that may eventually lead to the development of novel biomarkers and more effective management strategies to treat T2DM.

Keyword

Diabetes mellitus; Metagenomics; Microbiota; Vitamin K2

Figure

• 

  Fig. 1 Evaluation of community composition among samples. Panel shows non-metric multidimensional scaling (NMDS) ordination. Ordination plots were categorized by color according to the patient health status (Group 1) and by shape according to their diet (Group 2). T2DM, type 2 diabetes mellitus; LFD, low fiber diet; HFD, high fiber diet.

• 

  Fig. 2 Difference of functional profiles among samples. Panel shows difference in pathway richness (number of unique pathways) for (A) healthy and (B) type 2 diabetes mellitus (T2DM). Diabetic patients had higher richness of functional genes than that of healthy subjects (P<0.001) irrespective to differences in diet. LFD, low fiber diet; HFD, high fiber diet.

• 

  Fig. 3 Differential abundance testing of functional groups. (A) Panel shows pathways with significant relative abundance (P<0.001). (B) Log fold difference for significantly enriched pathways for type 2 diabetes mellitus (T2DM) and T2DM with high glycosylated hemoglobin (HbA1c) are PWY-5838 30 fold, PWY-2941 0.9 fold, and CRNFORCAT-PWY −0.9 fold in contrast to healthy and T2DM with low HbA1c.

• 

  Fig. 4 Covariance network of bacterial genera and metabolic pathways. Panel a shows a force-driven network based on the predicted covariances (analysis of variance with P<0.05) between the genera and metabolic pathways identified as statistically altered in type 2 diabetes mellitus as compared to healthy.

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