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Front Cell Infect Microbiol. 2016 Dec 9;6:179. doi: 10.3389/fcimb.2016.00179. eCollection 2016.

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

Author information

1
Medical Genomics Laboratory, CIPE/A.C. Camargo Cancer CenterSão Paulo, Brazil; Departamento de Bioquímica, Instituto de Química, Universidade de São PauloSão Paulo, Brazil; Curso de Pós-Graduação em Bioinformática, Universidade de São PauloSão Paulo, Brazil.
2
Medical Genomics Laboratory, CIPE/A.C. Camargo Cancer CenterSão Paulo, Brazil; Department of Pelvic Surgery, A.C. Camargo Cancer CenterSão Paulo, Brazil.
3
Department of Pelvic Surgery, A.C. Camargo Cancer Center São Paulo, Brazil.
4
Department of Pathology, A.C. Camargo Cancer Center São Paulo, Brazil.
5
Laboratory of Molecular Gynecology, Department of Gynecology, Medicine College, Federal University of São Paulo São Paulo, Brazil.
6
Centro de Oncologia Molecular, Hospital Sirio-Libanês São Paulo, Brazil.
7
Departamento de Alimentos e Nutrição Experimental, Faculdade de Ciências Farmacêuticas, Food Research Center (FoRC), Universidade de São Paulo São Paulo, Brazil.
8
Medical Genomics Laboratory, CIPE/A.C. Camargo Cancer CenterSão Paulo, Brazil; Department of Clinical Oncology, A.C. Camargo Cancer CenterSão Paulo, Brazil.
9
Laboratory of Computational Biology and Bioinformatics, A.C. Camargo Cancer Center São Paulo, Brazil.
10
Medical Genomics Laboratory, CIPE/A.C. Camargo Cancer Center São Paulo, Brazil.
11
Departamento de Bioquímica, Instituto de Química, Universidade de São PauloSão Paulo, Brazil; Biocomplexity Institute, Virginia TechBlacksburg, VA, USA.
12
Medical Genomics Laboratory, CIPE/A.C. Camargo Cancer CenterSão Paulo, Brazil; Laboratory of Neurosciences (LIM-27) Alzira Denise Hertzog Silva, Institute of Psychiatry, Faculdade de Medicina, Universidade de São PauloSão Paulo, Brazil.

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.

KEYWORDS:

16S rRNA gene sequencing; Bacterial diversity and community composition; Bacteroides fragilis; mucosa-associated microbiota; rectal cancer

PMID:
28018861
PMCID:
PMC5145865
DOI:
10.3389/fcimb.2016.00179
[Indexed for MEDLINE]
Free PMC Article

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