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. 2021 Feb 26:11:599734.
doi: 10.3389/fcimb.2021.599734. eCollection 2021.

Metagenome Analysis of Intestinal Bacteria in Healthy People, Patients With Inflammatory Bowel Disease and Colorectal Cancer

Yongshun Ma  1   2 , Yao Zhang  1   2 , Jianghou Xiang  3 , Shixin Xiang  1   2 , Yueshui Zhao  1   2 , Mintao Xiao  1   2 , Fukuan Du  1   2 , Huijiao Ji  1   2 , Parham Jabbarzadeh Kaboli  1   2 , Xu Wu  1   2 , Mingxing Li  1   2 , Qinglian Wen  4 , Jing Shen  1   2 , Zhongmin Yang  5 , Jing Li  5 , Zhangang Xiao  1   6
Affiliations

Metagenome Analysis of Intestinal Bacteria in Healthy People, Patients With Inflammatory Bowel Disease and Colorectal Cancer

Yongshun Ma et al. Front Cell Infect Microbiol. .

Erratum in

Abstract

Objectives: Several reports suggesting that the intestinal microbiome plays a key role in the development of inflammatory bowel disease (IBD) or colorectal cancer (CRC), but the changes of intestinal bacteria in healthy people, patients with IBD and CRC are not fully explained. The study aimed to investigate changes of intestinal bacteria in healthy subjects, patients with IBD, and patients with CRC.

Materials: We collected data from the European Nucleotide Archive on healthy people and patients with colorectal cancer with the study accession number PRJEB6070, PRJEB7774, PRJEB27928, PRJEB12449, and PRJEB10878, collected IBD patient data from the Integrated Human Microbiome Project from the Human Microbiome Project Data Portal. We performed metagenome-wide association studies on the fecal samples from 290 healthy subjects, 512 IBD patients, and 285 CRC patients. We used the metagenomics dataset to study bacterial community structure, relative abundance, functional prediction, differentially abundant bacteria, and co-occurrence networks.

Results: The bacterial community structure in both IBD and CRC was significantly different from healthy subjects. Our results showed that IBD patients had low intestinal bacterial diversity and CRC patients had high intestinal bacterial diversity compared to healthy subjects. At the phylum level, the relative abundance of Firmicutes in IBD decreased significantly, while the relative abundance of Bacteroidetes increased significantly. At the genus level, the relative abundance of Bacteroides in IBD was higher than in healthy people and CRC. Compared with healthy people and CRC, the main difference of intestinal bacteria in IBD patients was Bacteroidetes, and compared with healthy people and IBD, the main difference of intestinal bacteria in CRC patients was in Fusobacteria, Verrucomicrobia, and Proteobacteria. The main differences in the functional composition of intestinal bacteria in healthy people, IBD and CRC patients were L-homoserine and L-methionine biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis II, L-methionine biosynthesis I, and superpathway of L-lysine, L-threonine, and L-methionine biosynthesis I. The results of stratified showed that the abundance of Firmicutes, Bacteroidetes, and Actinobacteria involved in metabolic pathways has significantly changed. Besides, the association network of intestinal bacteria in healthy people, IBD, and CRC patients has also changed.

Conclusions: In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in IBD and CRC patients was significantly changed.

Keywords: colorectal cancer; fecal microbiota; inflammatory bowel disease; intestinal bacteria; metagenomics; taxonomic biomarkers.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Altered bacterial microbiota biodiversity and composition in IBD and CRC. (A) The composition of intestinal bacteria in the healthy group, IBD group, and CRC group was displayed by three phylogenetic trees. Different colors represent different phyla level classification, red for Actinobacteria, light green for Proteobacteria, pale purple for Bacteroidetes, azure for Firmicutes, orange for Verrucomicrobia, and gray for other phyla with low abundance. The letters indicate the genus with higher abundance. (B) The box plot showed the differences in the number of bacterial at the species level among the three groups. (C) The Venn diagram showed the common species and unique bacterial species of the three groups. (D) The Sankey chart showed the change of bacteria from healthy groups to IBD to CRC.
Figure 2
Figure 2
The difference in intestinal bacteria at the phylum and genus level among samples of different states. (A) The relative abundance of bacterial genera within the top 25 in healthy people, IBD, and CRC. (B) The boxplots showed the relative abundance of the top 25 genera in each group, sort the top 25 genera based on their mean values. (C) Bacterial relative abundance in the phylum level, including Firmicutes, Bacteroidetes, and Proteobacteria phylum. Green represents healthy controls, Purple represents IBD, and red represents CRC.
Figure 3
Figure 3
LEfSe analysis of the relative abundance of intestinal bacteria in healthy people, IBD, and CRC. (A) The node size represents the difference in relative abundance. Yellow nodes indicate bacteria with no significant differences in relative abundance. LEfSe cladogram in red for the taxa enriched in the CRC group, green for the taxa enriched in the healthy group, and blue for the taxa enriched in the IBD group. The meaning of shading color is the same as the node color. (B) The histogram showed all the different bacterial species and LDA scores, bacterial species with LDA score >2.0 and P < 0.05 were considered to be significantly discriminant. (C) The relative abundance of the top six bacterial species, each bar represents a patient sample.
Figure 4
Figure 4
The effect of the altered intestinal bacteria on predicted functional metabolic pathways. (A) PCA analysis of intestinal bacterial metabolic pathway, the blue color represents the healthy, yellow represents the IBD, green represents the CRC. (B) The scatter plot showed the functional differences between the three groups. The x-coordinate represents the corrected -log10(P-values), the y-coordinate represents the effect size, and the color depth represents the number of species participating in the pathway. (C) The boxplots showed the changes in the relative abundance of bacteria involved in the 10 differential pathways. The lower and upper hinges of boxplots presented in the Figures correspond to the 25th and 75th percentiles, respectively. The midline is the median. Data beyond the end of the whiskers are plotted individually. (D) The bar chart shows the functional differences between groups.
Figure 5
Figure 5
Stratified analyses of metabolic pathways by bacterial species. (A) The circle shows the pathways in which 16 differential bacteria species are involved. The black font represents the metabolic pathways. Red represents the bacterium that belongs to the phylum Bacteroidetes, green represents the bacterium that belongs to the phylum Firmicutes, brown represents the bacterium that belongs to the phylum Actinobacteria. (B) Log abundance for 10 major bacteria species compared between Healthy, IBD, and CRC cases. P values were determined by Kruskal–Wallis tests. The midline is the median, and the red diamond shape represents the mean values.
Figure 6
Figure 6
The association network of intestinal bacteria in different states. Each circle (node) represents a bacterial species, its color represents the bacterial phylum it belongs to and its size represents the number of direct edges that it has. Only significant correlations (−0.4
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