Southern Chinese populations harbour non-nucleatum Fusobacteria possessing homologues of the colorectal cancer-associated FadA virulence factor

Abstract

ObjectiveFusobacteria 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.MethodsPrevalence 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.ResultsIrrespective 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.ConclusionThe 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.

Extracellular vesicles of Fusobacterium nucleatum compromise intestinal barrier through targeting RIPK1-mediated cell death pathway

“…The adhesins FadA and Fap2 are also suggested to induce inflammatory responses in early tumorigenesis. 19 , 20 , 24 Therefore, EVs derived from Fn, an epithelial cell adhesion bacterium, may promote phenotypic polarization in macrophages to activate pro-inflammatory responses in the subcutaneous layer via these virulence factors.…”

“… 17 , 18 Recently, it was also associated with the progression of IBD, in which it was shown to produce many pathogenic factors, such as Fusobacterium autotransporter protein 2 (Fap2), adhesin A (FadA), and Fusobacterial outer membrane protein A (FomA) affecting the adherence or invasion of epithelial/endothelial cells. 19–21 In IBD patients, Fn species were found in areas of inflammation while these were absent in controls. Fn species are known to induce the expression of β-defensin and TNF-α and invasion of heterogeneous human epithelial colorectal adenocarcinoma in the Caco-2 cell lines.…”

Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19

“…These patients were laboratory-confirmed SARS-CoV-2 positive by quantitative reverse transcription PCR (RT-qPCR) performed on nasopharyngeal swabs collected by hospital staff. 13 Non-COVID-19 subjects were recruited before COVID-19 as part of a Hong Kong population gut microbiome survey recruited by advertisement 14 or non-disease controls from colonoscopy trials, 15 whereby subjects had a normal colonoscopy (stools collected several days before bowel preparation). Patients with COVID-19 were classified into four severity groups based on symptoms as reported by Wu et al 16…”

Gastric Adenocarcinomas and Signet-Ring Cell Carcinoma: Unraveling Gastric Cancer Complexity through Microbiome Analysis—Deepening Heterogeneity for a Personalized Therapy

“…Patescibacteria members are 3.4-times higher compared to ADC, however their relative abundance is very low (1.7%) and no data are reported in the literature regarding any potential association with cancer. On the contrary, Fusobacteria and Bacteroidetes, both including anaerobic bacteria, have been shown to be enriched in cancer, including colorectal, oral and head cancers [ 40 , 41 , 42 , 43 ]. This is interesting, in particular with regard to Fusobacteria; indeed, considering that tumor site distribution in SRCC and ADC was similar, we can speculate that its presence does not depend on the site, but is a possible biomarker for SRCC.…”