Enterotype Variations of the Healthy Human Gut Microbiome in Different Geographical Regions

Abstract

Enterotypes are used for classifying individuals based on the gut microbiome. A number of studies are available to find the Enterotypes in healthy individuals; however, most of them lack comparisons at the world level. We analyzed the healthy human gut microbiomes of 495 datasets available in the European Nucleotide Archive (ENA) database derived from fifteen countries from four continents. Firmicutes and Bacteroidetes were the two most abundant phyla in the healthy human gut, worldwide. A high ratio of Proteobacteriato Actinobacteria and a low abundance of Prevotella were identified as the indicators of IBD. Prevotella, Bacteroides, and Bifidobacterium were identified as the Enterotypes in the inter-continental comparisons. At the intra-continental level, two (Bacteroides and Ruminococcaceae), four (Faecalibacterium, Bacteroides, Prevotella, and Clostridiales), and two (Prevotella, Bacteroides/Bifidobacterium) Enterotypes were identified in the American, European, and Asian continents, respectively. In addition, a high abundance of the unknown genus of Ruminococcaeae was observed in the Colombian human gut microbiome. A substantial impact of the geographical distance was observed on human gut microbiome variations, demonstrating a cumulative effect of factors, including dietary habits, genetics, lifestyle, environment, and climate, etc.

Keywords: Enterotype; geographical factor; healthy human gut microbiome; inter-continental.

Figure 1

A flowchart of the methodology and bioinformatics tools used for the analyses.

Figure 2

A bar plot of the relative abundance of different phyla identified in the gut microbiomes of fifteen countries. X axis shows the contribution (%) of each phylum and Y axis shows the countries used in this study.

Figure 3

Alpha diversity box plots of the gut microbiome of the fifteen countries based on (A) Shannon index and (B) PD whole tree. X axis shows the name of the country and is arranged in continent wide order viz., Africa, Asia, Europe, and America along with the number of datasets, represented by n. Y axis shows the alpha diversity index.

Figure 4

Beta-diversity based Principal Component Analysis (PCA) plots of the human gut microbiomes of fifteen countries using (A) weighted and (B) unweighted unifrac distances. X, Y, and Z axes show PC1, PC2, and PC3 components respectively. PC1, PC2, and PC3 axes explain 33.28%, 9.27%, and 6.87%, respectively, in (A) and 9.62%, 5.3%, and 3.31%, respectively, in (B) of the human gut microbiome variations present among the datasets.

Figure 5

Visualization of three Enterotype clusters obtained from the Principal Coordinate Analysis (PCoA) identified in the healthy human gut microbiomes of 495 datasets from fifteen countries belonging to the four continents. The Enterotype taxa identified in cluster 1, cluster 2, and cluster 3 are Bifidobacterium, Prevotella, and Bacteroides, respectively.

Figure 6

Box plots of the relative abundances of the Enterotype taxa in each of the Enterotype clusters identified in the healthy human gut microbiomes of 495. X axis shows the three identified clusters and Y axis shows the relative abundance of the taxa. The statistical significance for the difference in the relative abundances in each Enterotype cluster is calculated using the Kruskal-Wallis test (p less than 0.05).

Figure 7

Visualization of the Enterotype clusters in Asian, American, and European datasets. The Enterotype taxa identified in clusters 1 and 2 of Asia are Bacteroides/Bifidobacterium (red) and Prevotella (green), respectively. The Enterotype taxa identified in clusters 1 and 2 of America are Bacteroides (red) and an unidentified genus of the family Ruminococcaceae (green), respectively. The Enterotype taxa identified in clusters 1, 2, 3, and 4 of Europe are Faecalibacterium (red),Bacteroides (green), Prevotella (blue), and an unidentified genus of the order Clostridiales (cyan), respectively. The Enterotype clusters in the human gut microbiome datasets have been identified using PCoA analysis.