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
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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.
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