Gut mucosal microbiome across stages of colorectal carcinogenesis

Abstract

Gut microbial dysbiosis contributes to the development of colorectal cancer (CRC). Here we catalogue the microbial communities in human gut mucosae at different stages of colorectal tumorigenesis. We analyse the gut mucosal microbiome of 47 paired samples of adenoma and adenoma-adjacent mucosae, 52 paired samples of carcinoma and carcinoma-adjacent mucosae and 61 healthy controls. Probabilistic partitioning of relative abundance profiles reveals that a metacommunity predominated by members of the oral microbiome is primarily associated with CRC. Analysis of paired samples shows differences in community configurations between lesions and the adjacent mucosae. Correlations of bacterial taxa indicate early signs of dysbiosis in adenoma, and co-exclusive relationships are subsequently more common in cancer. We validate these alterations in CRC-associated microbiome by comparison with two previously published data sets. Our results suggest that a taxonomically defined microbial consortium is implicated in the development of CRC.

Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

“…Fn is enriched in both the feces and colonic mucosa of colorectal cancer patients (3,5,8) and plays important roles in colorectal carcinogenesis (9,10). In our recent study, using 16S rRNA sequencing to catalog the microbial communities in human gut mucosa at different stages of colorectal tumorigenesis, Fusobacterium was also found to be enriched in colorectal tumors (11). Then by using metagenomics analysis to compare the fecal microbiome of 74 colorectal cancer patients and 54 healthy subjects, we have identified bacterial candidates that may serve as noninvasive biomarkers for colorectal cancer (12), including Fn, Bacteroides clarus (Bc), Roseburia intestinalis (Ri), Clostridium hathewayi (Ch), one undefined species (labeled as m7).…”

Targeting colorectal cancer-associated bacteria: A new area of research for personalized treatments

“…Studies comparing bacteria associated with tumor tissue and with tumor-adjacent mucosa of CRC patients, and bacteria associated with the mucosa of healthy patients have demonstrated the existence of a dysbiotic microbiota associated with CRC. [13][14][15][16][17] Although it is still difficult to identify a "typical" dysbiotic microbiota associated with CRC, the abnormal abundance of certain species in colonic tissues of CRC patients has been found in numerous studies. 13,15 Thus, studies of CRC have observed a specific enrichment in Fusobacterium and Bacteroides, 13,15,17 bacteria that can potentially play a role in colorectal carcinogenesis.…”

“…[13][14][15][16][17] Although it is still difficult to identify a "typical" dysbiotic microbiota associated with CRC, the abnormal abundance of certain species in colonic tissues of CRC patients has been found in numerous studies. 13,15 Thus, studies of CRC have observed a specific enrichment in Fusobacterium and Bacteroides, 13,15,17 bacteria that can potentially play a role in colorectal carcinogenesis. 18,19 In contrast, microbiota from healthy patients seems to be enriched in Bifidobacterium, 13 which are generally anti-inflammatory bacteria.…”

“…18,19 In contrast, microbiota from healthy patients seems to be enriched in Bifidobacterium, 13 which are generally anti-inflammatory bacteria. Interestingly, early signs of dysbiosis have been reported at the adenoma stage, 15 and there is a significant increase in some species (such as Bacteroides) from healthy to advanced adenoma and from advanced adenoma to carcinoma. 13 However, these studies were not able to identify adenoma-associated bacterial communities predictive of cancer progression.…”

“…They revealed enrichments in some bacterial functions (xenobiotic metabolism, utilization of polyamines and degradation of polycyclic aromatic compounds) in meta-communities associated with CRC. 15 These functions may lead to the production of protumorigenic metabolites, which are potentially important for cancer development. Thus, gut microbiota could be a new element to consider in the personalized treatment of CRC.…”