Multi-cohort analysis of colorectal cancer metagenome identified altered bacteria across populations and universal bacterial markers

Abstract

BackgroundAlterations of gut microbiota are associated with colorectal cancer (CRC) in different populations and several bacterial species were found to contribute to the tumorigenesis. The potential use of gut microbes as markers for early diagnosis has also been reported. However, cohort specific noises may distort the structure of microbial dysbiosis in CRC and lead to inconsistent results among studies. In this regard, our study targeted at exploring changes in gut microbiota that are universal across populations at species level.ResultsBased on the combined analysis of 526 metagenomic samples from Chinese, Austrian, American, and German and French cohorts, seven CRC-enriched bacteria (Bacteroides fragilis, Fusobacterium nucleatum, Porphyromonas asaccharolytica, Parvimonas micra, Prevotella intermedia, Alistipes finegoldii, and Thermanaerovibrio acidaminovorans) have been identified across populations. The seven enriched bacterial markers classified cases from controls with an area under the receiver-operating characteristics curve (AUC) of 0.80 across the different populations. Abundance correlation analysis demonstrated that CRC-enriched and CRC-depleted bacteria respectively formed their own mutualistic networks, in which the latter was disjointed in CRC. The CRC-enriched bacteria have been found to be correlated with lipopolysaccharide and energy biosynthetic pathways.ConclusionsOur study identified potential diagnostic bacterial markers that are robust across populations, indicating their potential universal use for non-invasive CRC diagnosis. We also elucidated the ecological networks and functional capacities of CRC-associated microbiota.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0451-2) contains supplementary material, which is available to authorized users.

Microbiota profile is different for early and invasive colorectal cancer and is consistent throughout the colon

“…The association of microbiota with the adenoma‐adenocarcinoma pathway has been the subject in several recent studies. Patients with invasive CRC have been consistently described with higher RA of Fusobacterium when compared to healthy controls . However, differences in the RA of Fusobacterium and other microbiota between healthy controls and patients with adenomas is less consistent.…”

“…Patients with invasive CRC have been consistently described with higher RA of Fusobacterium when compared to healthy controls. 3 However, differences in the RA of Fusobacterium and other microbiota between healthy controls and patients with adenomas is less consistent. There is evidence both for and against such differences.…”

“…In the past few years, several studies have found evidence that a specific gram‐negative anaerobic bacterium was consistently associated with CRC: the Fusobacterium nucleatum (Fn). This species has been shown to have an increased relative abundance (RA) in patients with CRC in many different cohorts . The question whether Fn plays a role in CRC carcinogenesis or if it is only a marker for CRC is still under debate.…”

“…This species has been shown to have an increased relative abundance (RA) in patients with CRC in many different cohorts. 2,3 The question whether Fn plays a role in CRC carcinogenesis or if it is only a marker for CRC is still under debate. Some studies advocate it is solely a marker as it has only been associated with CRC as opposed to advanced adenomas.…”

HARMONIES: A Hybrid Approach for Microbiome Networks Inference via Exploiting Sparsity

“…This study suggested that P. anaerobius directly interacted with colonic epithelial cells and also promoted CRC by modifying the tumor immune microenvironment. While the causal role of the species Parvimonas micra (P. micra) has not been biologically validated, multiple clinical studies reported an elevated level of P. micra in CRC patients Yu et al (2017); Purcell et al (2017); Dai et al (2018). Of interest, Parvimonas were closely associated with animal-based diets, which have previously been shown to be significantly associated with increased risk for CRC Chan et al (2011).…”