Gut metagenomes of type 2 diabetic patients have characteristic single-nucleotide polymorphism distribution in Bacteroides coprocola

Abstract

Background: Gut microbes play a critical role in human health and disease, and researchers have begun to characterize their genomes, the so-called gut metagenome. Thus far, metagenomics studies have focused on genus- or species-level composition and microbial gene sets, while strain-level composition and single-nucleotide polymorphism (SNP) have been overlooked. The gut metagenomes of type 2 diabetes (T2D) patients have been found to be enriched with butyrate-producing bacteria and sulfate reduction functions. However, it is not known whether the gut metagenomes of T2D patients have characteristic strain patterns or SNP distributions.

Findings: We downloaded public gut metagenome datasets from 170 T2D patients and 174 healthy controls and performed a systematic comparative analysis of their metagenome SNPs. We found that Bacteroides coprocola, whose relative abundance did not differ between the groups, had a characteristic distribution of SNPs in the T2D patient group. We identified 65 genes, all in B. coprocola, that had remarkably different enrichment of SNPs. The first and sixth ranked genes encode glycosyl hydrolases (GenBank accession EDU99824.1 and EDV02301.1). Interestingly, alpha-glucosidase, which is also a glycosyl hydrolase located in the intestine, is an important drug target of T2D. These results suggest that different strains of B. coprocola may have different roles in human gut and a specific set of B. coprocola strains are correlated with T2D.

Keywords: Bacteria; Metagenome; Phylogenetic analysis; SNP enrichment; Type 2 diabetes.

Fig. 1

Phylogenetic tree based on B. coprocola SNPs. Red and blue branches indicate T2D samples and HC (i.e., normal) samples, respectively. The boxplot graph of SNP density for B. coprocola in each sample group is shown in the inset graph

Fig. 2

Phylogenetic trees and SNP distributions of the genes EDU99824.1 (a) and EDV02303.1 (b). Samples in clusters 1 and 2 are indicated by light blue and pink shading, respectively. The lines aligned to tree leaves represent corresponding gene sequences with sufficiently covered reads, with missense (red dot) and silent (green dot) SNPs indicated. The bar graphs above the gene sequences show the number of SNPs found at each site (aligned to each bar) in the T2D group (red bars above the axis) and the HC group (blue bars below the axis). Fisher’s exact test results for 2 × 2 contingency tables are shown in the upper left of each panel