J Bacteriol Virol.  2019 Dec;49(4):162-175. 10.4167/jbv.2019.49.4.162.

Analysis of Intestinal Mucosal Microbiome Changes before and after Chemoradiation in Locally Advanced Rectal Cancer Patients

Affiliations
  • 1Dasa Geriatric Hospital, Daegu, Korea.
  • 2Department of Surgery, School of Medicine, Keimyung University and Dongsan Medical Center, Daegu, Korea. sabiston0000@hanmail.net
  • 3Department of Immunology, School of Medicine, Keimyung University, Daegu, Korea.

Abstract

PURPOSE
Dysbiosis of gut microbiota has been reported to participate in the pathogenesis of colorectal cancer, but changes in microbiota due to radiotherapy have not been studied. In this study, we tried to elucidate the changes in the microbiome in rectal cancer after chemoradiotherapy using RNA sequencing analysis.
MATERIALS AND METHODS
We included 11 pairs of human rectal cancer tissues before and after irradiation between August 2016 and December 2017 and performed RNA sequencing analysis. Mapped reads to human reference genomes were used for pair-wise transcriptome comparisons, and unmapped (non-human) reads were then mapped to bacterial marker genes using PathSeq.
RESULTS
At microbiome level, interindividual variability of mucosal microbiota was greater than the change in microbial composition during radiotherapy. This indicates that rapid homeostatic recovery of the mucosal microbial composition takes place short after radiotherapy. At single microbe level, Prevotella and Fusobacterium, which were identified as important causative microbes of the initiation and progression of rectal cancer were decreased by radiotherapy. Moreover, changes in Prevotella were associated with changes in the human transcriptome of rectal cancer. We also found that there was a gene cluster that increased and decreased in association with changes in microbial composition by chemoradiation.
CONCLUSION
This study revealed changes in tumor-associated microbial community by irradiation in rectal cancer. These findings can be used to develop a new treatment strategy of neoadjuvant therapy for locally advanced rectal cancer by overcoming radio-resistance or facilitating radio-sensitivity.

Keyword

Microbiome; Rectal cancer; Radiotherapy

MeSH Terms

Chemoradiotherapy
Colorectal Neoplasms
Dysbiosis
Fusobacterium
Gastrointestinal Microbiome
Genes, vif
Genome
Humans
Microbiota*
Neoadjuvant Therapy
Prevotella
Radiotherapy
Rectal Neoplasms*
Sequence Analysis, RNA
Transcriptome
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