The gut microbiota in conventional and serrated precursors of colorectal cancer

Abstract

BackgroundColorectal cancer is a heterogeneous disease arising from at least two precursors—the conventional adenoma (CA) and the serrated polyp. We and others have previously shown a relationship between the human gut microbiota and colorectal cancer; however, its relationship to the different early precursors of colorectal cancer is understudied. We tested, for the first time, the relationship of the gut microbiota to specific colorectal polyp types.ResultsGut microbiota were assessed in 540 colonoscopy-screened adults by 16S rRNA gene sequencing of stool samples. Participants were categorized as CA cases (n = 144), serrated polyp cases (n = 73), or polyp-free controls (n = 323). CA cases were further classified as proximal (n = 87) or distal (n = 55) and as non-advanced (n = 121) or advanced (n = 22). Serrated polyp cases were further classified as hyperplastic polyp (HP; n = 40) or sessile serrated adenoma (SSA; n = 33). We compared gut microbiota diversity, overall composition, and normalized taxon abundance among these groups.CA cases had lower species richness in stool than controls (p = 0.03); in particular, this association was strongest for advanced CA cases (p = 0.004). In relation to overall microbiota composition, only distal or advanced CA cases differed significantly from controls (p = 0.02 and p = 0.002). In taxon-based analysis, stool of CA cases was depleted in a network of Clostridia operational taxonomic units from families Ruminococcaceae, Clostridiaceae, and Lachnospiraceae, and enriched in the classes Bacilli and Gammaproteobacteria, order Enterobacteriales, and genera Actinomyces and Streptococcus (all q < 0.10). SSA and HP cases did not differ in diversity or composition from controls, though sample size for these groups was small. Few taxa were differentially abundant between HP cases or SSA cases and controls; among them, class Erysipelotrichi was depleted in SSA cases.ConclusionsOur results indicate that gut microbes may play a role in the early stages of colorectal carcinogenesis through the development of CAs. Findings may have implications for developing colorectal cancer prevention therapies targeting early microbial drivers of colorectal carcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-016-0218-6) contains supplementary material, which is available to authorized users.

Moderate alteration to gut microbiota brought by colorectal adenoma resection

“…Streptococcus is reported to increase in the intestine of adenoma patients and promote colorectal carcinogenesis. 23 Streptococcus gallolyticus subspecies gallolyticus seems more closely associated with colorectal tumorigenesis and can result in adenomaassociated infectious streptococcal endocarditis. 24,25 The microbial role in tumorigenesis is related to direct contact with cells as well as increased levels of β-catenin, c-Myc, and PCNA.…”

Gut microbiota in patients after surgical treatment for colorectal cancer

“…Emerging evidence suggests that microbial dysbiosis in the human gut may be an important contributing environmental factor in CRC (Sanapareddy et al, 2012;Wang et al, 2012;Chen et al, 2013;Peters et al, 2016;Sze et al, 2017). Marked attention has been paid to the delineation of the gut microbiota throughout different stages of colorectal carcinogenesis (Feng et al, 2015;Nakatsu et al, 2015).…”

Parabacteroides distasonis attenuates toll‐like receptor 4 signaling and Akt activation and blocks colon tumor formation in high‐fat diet‐fed azoxymethane‐treated mice

“…There are 135,000 new cases diagnosed and approximately 50,000 deaths from this disease annually in the US alone. 1 Findings that the gut microbiome differs between individuals with CRC and healthy controls, 2,3 and that alterations are already present in those with precancerous adenomas, [4][5][6][7] suggest that dysbiosis of the gut microbiome could play an etiologic role in CRC. A causal role for gut microbiota in colorectal tumorigenesis is further supported by observations that gut microbiota from tumor-bearing mice 8 or specific human gut bacterial communities 9 promote colon tumorigenesis when inoculated into germ-free mice.…”