Abstract
ObjectivesSeveral 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.MaterialsWe 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.ResultsThe 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.ConclusionsIn conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in IBD and CRC patients was significantly changed.
Highlights
The incidence and mortality rate of inflammatory bowel disease (IBD) and colorectal cancer (CRC) are very high and increase year by year (Ferlay et al, 2015; Dahlhamer et al, 2016)
The intestinal bacteria of healthy people, IBD and CRC patients was dominated by four phyla: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, among which, Firmicutes and Bacteroidetes are the most abundant bacteria in the gut microbiota (Figure 1A)
At the species level, compared with CRC patients and healthy controls, the species counts of intestinal bacteria in patients with IBD decreased
Summary
The incidence and mortality rate of IBD and CRC are very high and increase year by year (Ferlay et al, 2015; Dahlhamer et al, 2016). There is growing evidence that gut microbes play an important role in IBD and CRC (Ni et al, 2017; Kwong et al, 2018). It is well-known that an altered gut microbiota composition is associated with IBD (Manichanh et al, 2012). Patients with IBD are at increased risk of developing CRC in later life, and aberrant immune responses to penetrating commensal microbes may play key roles in promoting disease progression, but the reasons for this are not fully explained (Gillen et al, 1994; Munkholm, 2003; Rutter et al, 2004; Yu, 2018; Clarke and Feuerstein, 2019). It is worthwhile to study the changes in intestinal bacteria from healthy people to IBD and CRC, which will contribute to further understanding of the pathogenesis of intestinal bacteria in diseases
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