Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Community Profiling

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.

Pretreatment with probiotic Bifico ameliorates colitis‐associated cancer in mice: Transcriptome and gut flora profiling

“…14,[47][48][49] Odoribacter is also reported to markedly bloom in AOM/ DSS-induced CRC mice and patients with rectal cancer. 42,50 As shown in our results, the significant enrichment of Desulfovibrio, Mucispirillum, and Odoribacter in the Model group was partly removed by treatment with Bifico, suggesting that Bifico could relieve inflammation and decrease tumor formation by inhibiting these colitogenic bacteria. We also detected a tremendous expansion of the genus Lactobacillus, a member of the Bifico bacterial group.…”

“…As previous studies described, Desulfovibrio had the capacity to degrade sulfate and produce high levels of hydrogen sulfide, which is regarded as a genotoxic agent that might play a role in colitis and colonic tumorigenesis . Desulfovibrio also displays a flourish of relative abundance in IBD colon tissues and in patients with adenoma and rectal cancer . However, most studies have shown that the abundance of Desulfovibrio in the intestinal tract of colon cancer patients does not increase .…”

“…Mucispirillum , with increasing abundance in DSS‐treated mice and natural killer T cell‐deficient mice, is recognized as opportunistic pathogen that may fuel inflammation . Odoribacter is also reported to markedly bloom in AOM/DSS‐induced CRC mice and patients with rectal cancer …”

“…41 Desulfovibrio also displays a flourish of relative abundance in IBD colon tissues and in patients with adenoma and rectal cancer. 14,[42][43][44] However, most studies have shown that the abundance of Desulfovibrio in the intestinal tract of colon cancer patients does not increase. 45,46 Considering its role in triggering colonic inflammation, Desulfovibrio may be of larger significance in CAC initiation and progression than in sporadic colorectal cancer.…”

The differential distribution of bacteria between cancerous and noncancerous ovarian tissues in situ

“…The genus Photorhabdus has been related to soft tissue infection and bacteremia(14). The genus Dorea exists in human gut mucosa and tumor tissue and is related to colorectal cancer(15, 16). Another genus was first found present in the human body and had a potential association with ovarian cancer.…”