Abstract
Sporadic and inflammatory forms of colorectal cancer (CRC) account for more than 80% of cases. Recent publications have shown mechanistic evidence for the involvement of gut bacteria in the development of both CRC-forms. Whereas, colon and rectal cancer have been routinely studied together as CRC, increasing evidence show these to be distinct diseases. Also, the common use of fecal samples to study microbial communities may reflect disease state but possibly not the tumor microenvironment. We performed this study to evaluate differences in bacterial communities found in tissue samples of 18 rectal-cancer subjects when compared to 18 non-cancer controls. Samples were collected during exploratory colonoscopy (non-cancer group) or during surgery for tumor excision (rectal-cancer group). High throughput 16S rRNA amplicon sequencing of the V4–V5 region was conducted on the Ion PGM platform, reads were filtered using Qiime and clustered using UPARSE. We observed significant increases in species richness and diversity in rectal cancer samples, evidenced by the total number of OTUs and the Shannon and Simpson indexes. Enterotyping analysis divided our cohort into two groups, with the majority of rectal cancer samples clustering into one enterotype, characterized by a greater abundance of Bacteroides and Dorea. At the phylum level, rectal-cancer samples had increased abundance of candidate phylum OD1 (also known as Parcubacteria) whilst non-cancer samples had increased abundance of Planctomycetes. At the genera level, rectal-cancer samples had higher abundances of Bacteroides, Phascolarctobacterium, Parabacteroides, Desulfovibrio, and Odoribacter whereas non-cancer samples had higher abundances of Pseudomonas, Escherichia, Acinetobacter, Lactobacillus, and Bacillus. Two Bacteroides fragilis OTUs were more abundant among rectal-cancer patients seen through 16S rRNA amplicon sequencing, whose presence was confirmed by immunohistochemistry and enrichment verified by digital droplet PCR. Our findings point to increased bacterial richness and diversity in rectal cancer, along with several differences in microbial community composition. Our work is the first to present evidence for a possible role of bacteria such as B. fragilis and the phylum Parcubacteria in rectal cancer, emphasizing the need to study tissue-associated bacteria and specific regions of the gastrointestinal tract in order to better understand the possible links between the microbiota and rectal cancer.
Highlights
The gut microbiota is a vast and diverse ensemble of bacteria and other microorganisms that work together to help digestion, produce vitamins, fatty acids, amino acids and other bioactive compounds, and participate in the regulation of our immune, metabolic, and neurological systems (Shapiro et al, 2014; Boulangé et al, 2016)
In face of the microbiota gradient found in the human digestive tract (Zhang et al, 2014; Gao et al, 2015; Flemer et al, 2016) and the possibility that tissue-associated microorganisms could play a more direct role in immunomodulation and cancer development, we investigated bacterial populations present in tissue biopsies, which may be relevant to pathological processes
Effect size analysis (Kelly et al, 2015) between both groups revealed an ω2 ranging from 0.13 to 0.26, depending on the metric of pairwise distance, with PERMANOVA p-values
Summary
The gut microbiota is a vast and diverse ensemble of bacteria and other microorganisms that work together to help digestion, produce vitamins, fatty acids, amino acids and other bioactive compounds, and participate in the regulation of our immune, metabolic, and neurological systems (Shapiro et al, 2014; Boulangé et al, 2016). The understanding of our microbiota, together with the determination of its composition when contrasting healthy vs diseased states allows the identification of microorganism disturbances that are possibly related to disease development and, offers a new approach for diagnosis as well as preventive and therapeutic interventions. Tobacco and alcohol consumption, which have been linked to the development of a number of pathological states (such as obesity, allergy, diabetes, Crohn’s disease, irritable colon syndrome, and cancer) are known to drive microbiome alterations and lead to dysbiosis (Turnbaugh et al, 2009; Leclercq et al, 2014; Allais et al, 2016). The emerging concept that cancer needs to be studied considering the complex tumor microenvironment, which includes components such as tumor cells, the surrounding microenviroment and the microbiome, may aid in the development and improvement of cancer treatment, including immunotherapy (Pitt et al, 2016)
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