Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers

Abstract

Despite a long-suspected role in the development of human colorectal cancer (CRC), the composition of gut microbiota in CRC patients has not been adequately described. In this study, fecal bacterial diversity in CRC patients (n=46) and healthy volunteers (n=56) were profiled by 454 pyrosequencing of the V3 region of the 16S ribosomal RNA gene. Both principal component analysis and UniFrac analysis showed structural segregation between the two populations. Forty-eight operational taxonomic units (OTUs) were identified by redundancy analysis as key variables significantly associated with the structural difference. One OTU closely related to Bacteroides fragilis was enriched in the gut microbiota of CRC patients, whereas three OTUs related to Bacteroides vulgatus and Bacteroides uniformis were enriched in that of healthy volunteers. A total of 11 OTUs belonging to the genera Enterococcus, Escherichia/Shigella, Klebsiella, Streptococcus and Peptostreptococcus were significantly more abundant in the gut microbiota of CRC patients, and 5 OTUs belonging to the genus Roseburia and other butyrate-producing bacteria of the family Lachnospiraceae were less abundant. Real-time quantitative PCR further validated the significant reduction of butyrate-producing bacteria in the gut microbiota of CRC patients by measuring the copy numbers of butyryl-coenzyme A CoA transferase genes (Mann-Whitney test, P<0.01). Reduction of butyrate producers and increase of opportunistic pathogens may constitute a major structural imbalance of gut microbiota in CRC patients.

Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome

“…An altered presence of specific micro-organisms has been associated with a number of diseases of the gastro intestinal tract (GIT), such as inflammatory bowel disease (IBD) [7], irritable bowel syndrome (IBS, #14) [8,9] and CRC [10][11][12]. While its role remains unclear, Helicobacter pylori has long been associated with CRC [13] and intraepithelial Escherichia coli was also found to be present in the colonic mucosa of tumour and normal tissue from CRC patients [14].…”

“…These micro-organisms are thought to create a microenvironment more favourable to CRC development [16]. It now seems that not only can the bacterial composition of the gut assist initiation and progression of colorectal tumours, but also that tumours can affect the representation of bacteria in their vicinity [10,12,17].…”

Bacterial communities of Beijing surface waters as revealed by 454 pyrosequencing of the 16S rRNA gene

“…The main advantages of 454 pyrosequencing are a much lower cost per base, the omission of a plasmid cloning step, a large amount of sequence data per run, and long read lengths with an average of up to 400 bps (Glenn 2011;Margulies et al 2005). With the implementation of 454 pyrosequencing, the microbial diversity and abundance in various ecosystems have been revealed, such as soil (Eilers et al 2012), marine water (Qian et al 2011), drinking water (Hong et al 2010), activated sludge samples (Sánchez et al 2013), hot springs (Hou et al 2013), and human feces (Wang et al 2012a).…”

Microbiome

“…Les trois patients considérés comme nonrépondeurs (score composite) avaient été inclus dans les essais cliniques sur la base d 'un [2]. Firmicutes, Bacteroidetes et gènes dans le développement du cancer colorectal chez l'humain n'est pas établie.…”