In Silico Comparison Shows that the Pan-Genome of a Dairy-Related Bacterial Culture Collection Covers Most Reactions Annotated to Human Microbiomes

Abstract

The diversity of the human microbiome is positively associated with human health. However, this diversity is endangered by Westernized dietary patterns that are characterized by a decreased nutrient variety. Diversity might potentially be improved by promoting dietary patterns rich in microbial strains. Various collections of bacterial cultures resulting from a century of dairy research are readily available worldwide, and could be exploited to contribute towards this end. We have conducted a functional in silico analysis of the metagenome of 24 strains, each representing one of the species in a bacterial culture collection composed of 626 sequenced strains, and compared the pathways potentially covered by this metagenome to the intestinal metagenome of four healthy, although overweight, humans. Remarkably, the pan-genome of the 24 strains covers 89% of the human gut microbiome's annotated enzymatic reactions. Furthermore, the dairy microbial collection covers biological pathways, such as methylglyoxal degradation, sulfate reduction, g-aminobutyric (GABA) acid degradation and salicylate degradation, which are differently covered among the four subjects and are involved in a range of cardiometabolic, intestinal, and neurological disorders. We conclude that microbial culture collections derived from dairy research have the genomic potential to complement and restore functional redundancy in human microbiomes.

Keywords: dairy microbiome; diversity; health; human gut microbiome.

Figure 1

Relationship between the number of identified genes and the number of enzyme commission (EC)-annotated genes per Liebefeld collection strain. Strains from the Liebefeld selection are highlighted with a larger symbol. Each species is represented by a unique symbol and color. A plot that includes the 24 human gut bacteria randomly selected from Zou et al. [43] is available in Figure S1.

Figure 2

Boxplot of the coverage of the 190 MetaCyc superpathways by each of the 24 strains of the Liebefeld selection (blue, referred to by their species name) and the four human microbiomes (red, MH0001-4), the Liebefeld collection (green), and the Liebefeld random selection (violet). Core-genomes are colored in a lighter and pan-genomes in a darker shade of the corresponding color. The strains or sets of strains are sorted in ascending order according to their mean superpathway coverage, indicated by a black dot. Above each boxplot, three numbers indicate how many superpathways are not covered (top row), partially covered (middle row) and completely covered (bottom row). An analogous plot comparing the Liebefeld selection strains to the 24 human gut bacteria randomly selected from Zou et al. [43] is available in Figure S3.

Figure 3

Overview of the biochemical potential of the 24 strains of Liebefeld selection (blue, referred to by their species name), the four human microbiomes (red, MH0001-4), the Liebefeld collection (green), and the Liebefeld random selection (violet). Core-genomes are colored in a lighter- and pan-genomes in a darker shade of the corresponding color. The Y-axis denotes the 190 superpathways of MetaCyc. The dendrogram of both axes resulted from hierarchical clustering. The colors of the heatmap denote superpathway coverage and range from white (0%) to black (100%). An analogous plot comparing the Liebefeld selection strains to the 24 human gut bacteria randomly selected from Zou et al. [43] is available in Figure S4.

Figure 4

Clustered heatmap of the number of shared unique EC numbers (uECs) of 24 strains of Liebefeld selection (blue, referred to by their species name), the four human microbiomes (red, MH0001-4), the Liebefeld collection (green), and the Liebefeld random selection (violet). Core-genomes are colored in a lighter- and pan-genomes in a darker shade of the corresponding color. The total number of uECs annotated to a species/metagenome can be read from the antidiagonal line, where the same species/metagenome intersect. The dendrogram of both axes resulted from hierarchical clustering. An analogous plot comparing the Liebefeld selection strains to the 24 human gut bacteria randomly selected from Zou et al. [43] is available in Figure S5.

Figure 5

Venn diagrams of the shared unique EC numbers (uECs) between the average human microbiome (red) and the average Liebefeld selection strain (light blue), the Liebefeld selection pan-genome (dark blue) and the Liebefeld collection pan-genome (green).

Figure 6

Overview of the biochemical potential of the 24 strains of Liebefeld selection (blue, referred to by their species name) and the four human microbiomes (red, MH0001-4), the Liebefeld collection (green), and the Liebefeld random selection (violet), for the fifteen superpathways with the highest variance amongst the human microbiomes. Core-genomes are colored in a lighter and pan-genomes in a darker shade of the corresponding color. The Y-axis denotes these 15 superpathways. The dendrogram of both axes resulted from hierarchical clustering. The colors of the heatmap denote superpathway coverage and range from white (0%) to black (100%). An analogous plot comparing the Liebefeld selection strains to the 24 human gut bacteria randomly selected from Zou et al. [43] is available in Figure S6.