Fusobacterium species are components of the normal microbiota of the oral cavity, gastrointestinal tract, and female genital tract. They are increasingly recognized as causative agents of oral, laryngeal, and tonsillar infections. Several fusobacterial species are involved in infections, with F. necrophorum and F. nucleatum being the most commonly cultured subtypes. In this study, we aimed to investigate clinical and prognostic differences in terms of mortality and association with malignancy between F. necrophorum and F. nucleatum detected by culture and 16S rRNA gene sequencing. This is a systematic, comparative, retrospective, non-interventional study. Data were extracted from the Department of Clinical Microbiology, Region Zealand, Denmark: all patients with F. necrophorum or F. nucleatum detected by culture or 16S rRNA gene sequencing from 1st of January 2010 to 30th of June 2015 were included. In total, F. necrophorum was detected in samples from 75 patients, and F. nucleatum in samples from 68 patients (total: n = 143). Thirteen patients had a current cancer diagnosis at the time of fusobacterial sampling. Multivariate analyses revealed a significant association of “current cancer” with 30-day mortality. Fusobacterial subtype was not associated with mortality neither in overall nor in subgroups with or without current cancer. Despite differences in clinical disease pattern between F. necrophorum and F. nucleatum, mortality was unaffected by fusobacterial subtype. Mortality was significantly related to comorbidity, especially a current diagnosis of cancer. Our data highlights the current debate whether fusobacterial involvement in cancer may have disease-altering properties, rather than being opportunistic pathogens secondary to cancer disease.
Fusobacteria F. necrophorumF. nucleatumInfections Mortality
This is a preview of subscription content, log in to check access.
The authors wish to thank Jørgen Harald Engberg for his revision of the manuscript.
KJ analyzed data and drafted the manuscript; SK provided data, did lab work, and revised the manuscript; NG compiled all data and revised the manuscript; XN did lab work and wrote part of the methods section as well as revised the manuscript; TB conceptualized the manuscript and revised it and UB conceptualized the manuscript, analyzed data, and revised the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest to report.
Access to data
Access to data will be granted by request to those eligible for this.
Han YW (2015) Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol 23:141–147CrossRefGoogle Scholar
Bank S, Jensen A, Nielsen HM, Kristensen LH, Voldstedlund M, Prag J (2016) Fusobacterium necrophorum findings in Denmark from 2010 to 2014 using data from the Danish microbiology database. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 124(12):1087–1092CrossRefGoogle Scholar
Holm K, Bank S, Nielsen H, Kristensen LH, Prag J, Jensen A (2016) The role of Fusobacterium necrophorum in pharyngotonsillitis - a review. Anaerobe 42:89–97CrossRefGoogle Scholar
Huggan PJ, Murdoch DR (2008) Fusobacterial infections: clinical spectrum and incidence of invasive disease. J Infect 57(4):283–289CrossRefGoogle Scholar
Johannesen K, Dessau R, Heltberg O, Bodtger U (2016) Bad news itself or just the messenger? The high mortality of Fusobacterium spp. infections is related to disseminated malignancy and other comorbidities. Eur Clin Respir J 3:30287CrossRefGoogle Scholar
Ehlers Klug T, Rusan M, Fuursted K, Ovesen T (2009) Fusobacterium necrophorum: most prevalent pathogen in peritonsillar abscess in Denmark. Clin Infect Dis 49(10):1467–1472CrossRefGoogle Scholar
Johannesen K, Bodtger U, Heltberg O (2014) Lemierre’s syndrome: the forgotten disease. J Thromb Thrombolysis 37(3):246–248CrossRefGoogle Scholar
Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW (2013) Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe 14(2):195–206CrossRefGoogle Scholar
Patel M (2013) 16S rDNA PCR in diagnosis of Lemierre’s syndrome. Lancet Infect Dis 13(3):197CrossRefGoogle Scholar
Gleesen AS, Grarup C, Dargis R, Andresen K, Christensen JJ, Kemp M (2008) PCR and DNA sequencing in establishing the aetiology of bacterial infections in children. APMIS: acta pathologica, microbiologica, et immunologica Scandinavica 116(9):811–815CrossRefGoogle Scholar
Mitsuhashi K, Nosho K, Sukawa Y, Matsunaga Y, Ito M, Kurihara H et al (2015) Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis. Oncotarget 6(9):7209–7220CrossRefGoogle Scholar
Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J et al (2012) Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 22(2):299–306CrossRefGoogle Scholar
Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM et al (2012) Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22(2):292–298CrossRefGoogle Scholar
McCoy AN, Araujo-Perez F, Azcarate-Peril A, Yeh JJ, Sandler RS, Keku TO (2013) Fusobacterium is associated with colorectal adenomas. PLoS One 8(1):e53653CrossRefGoogle Scholar
Flanagan L, Schmid J, Ebert M, Soucek P, Kunicka T, Liska V et al (2014) Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. Eur J Clin Microbiol Infect Dis 33(8):1381–1390CrossRefGoogle Scholar
Abed J, Maalouf N, Parhi L, Chaushu S, Mandelboim O, Bachrach G (2017) Tumor targeting by Fusobacterium nucleatum: a pilot study and future perspectives. Front Cell Infect Microbiol 7:295CrossRefGoogle Scholar
Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, Michaud M et al (2013) Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14(2):207–215CrossRefGoogle Scholar
Nosho K, Sukawa Y, Adachi Y, Ito M, Mitsuhashi K, Kurihara H et al (2016) Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. World J Gastroenterol 22(2):557–566CrossRefGoogle Scholar
Ahn J, Sinha R, Pei Z, Dominianni C, Wu J, Shi J et al (2013) Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst 105(24):1907–1911CrossRefGoogle Scholar