Article Text

Download PDFPDF

Original research
Southern Chinese populations harbour non-nucleatum Fusobacteria possessing homologues of the colorectal cancer-associated FadA virulence factor
  1. Yun Kit Yeoh1,2,
  2. Zigui Chen1,2,
  3. Martin C S Wong1,3,
  4. Mamie Hui1,2,
  5. Jun Yu1,4,
  6. Siew C Ng1,4,
  7. Joseph J Y Sung4,
  8. Francis K L Chan1,4,
  9. Paul K S Chan1,2
  1. 1Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Shatin, Hong Kong
  2. 2Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong
  3. 3Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
  4. 4Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
  1. Correspondence to Professor Paul K S Chan, Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong; paulkschan{at}cuhk.edu.hk

Abstract

Objective Fusobacteria are not common nor relatively abundant in non-colorectal cancer (CRC) populations, however, we identified multiple Fusobacterium taxa nearly absent in western and rural populations to be comparatively more prevalent and relatively abundant in southern Chinese populations. We investigated whether these represented known or novel lineages in the Fusobacterium genus, and assessed their genomes for features implicated in development of cancer.

Methods Prevalence and relative abundances of fusobacterial species were calculated from 3157 CRC and non-CRC gut metagenomes representing 16 populations from various biogeographies. Microbial genomes were assembled and compared with existing reference genomes to assess novel fusobacterial diversity. Phylogenetic distribution of virulence genes implicated in CRC was investigated.

Results Irrespective of CRC disease status, southern Chinese populations harboured increased prevalence (maximum 39% vs 7%) and relative abundances (average 0.4% vs 0.04% of gut community) of multiple recognised and novel fusobacterial taxa phylogenetically distinct from Fusobacterium nucleatum. Genomes assembled from southern Chinese gut metagenomes increased existing fusobacterial diversity by 14.3%. Homologues of the FadA adhesin linked to CRC were consistently detected in several monophyletic lineages sister to and inclusive of F. varium and F. ulcerans, but not F. mortiferum. We also detected increased prevalence and relative abundances of F. varium in CRC compared with non-CRC cohorts, which together with distribution of FadA homologues supports a possible association with gut disease.

Conclusion The proportion of fusobacteria in guts of southern Chinese populations are higher compared with several western and rural populations in line with the notion of environment/biogeography driving human gut microbiome composition. Several non-nucleatum taxa possess FadA homologues and were enriched in CRC cohorts; whether this imposes a risk in developing CRC and other gut diseases deserves further investigation.

  • colonic bacteria
  • colorectal cancer
  • intestinal microbiology
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

View Full Text

Statistics from Altmetric.com

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Footnotes

  • Contributors YKY designed the study, analysed data and wrote the manuscript; ZC performed laboratory work; MCSW recruited subjects and edited the manuscript; MH revised the manuscript; JY, SCN and JJYS recruited subjects and acquired data; FKLC initiated the subject recruitment drive and provided funding; PKSC obtained funding, designed recruitment plan, recruited subjects, supervised the study and edited the manuscript.

  • Funding This study was supported by a seed fund for gut microbiota research provided by the Faculty of Medicine, The Chinese University of Hong Kong.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval This study has been approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (reference number 2016.707). Written informed consent was obtained from all participants prior to collecting stool samples.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository. https://www.ncbi.nlm.nih.gov/bioproject/PRJNA557323. Gut metagenome and fusobacterial isolate genome sequence data are available in the Sequence Read Archive (SRA) under BioProject accession PRJNA557323.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.