A Simple and Novel Fecal Biomarker for Colorectal Cancer: Ratio of Fusobacterium Nucleatum to Probiotics Populations, Based on Their Antagonistic Effect

Guo, Songhe; Li, Linfang; Xu, Banglao; Mang-hui, LI; Zeng, Qiuyao; Han, Xiao; Xue, Yingwei; Wu, Yixian; Wang, Yidan; Liu, Wanli; Zhang, Ge

doi:10.1373/clinchem.2018.289728

Cited by 127 publications

(120 citation statements)

References 34 publications

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“…For cohorts with larger sample size (>200), the diagnostic ability of fecal F. nucleatum for CRC was better than cohorts with smaller sample size, with lower sensitivity. And the heterogeneity of sensitivity, positive DLR, and negative DLR all dropped sharply.…”

Section: Resultsmentioning

confidence: 95%

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Fecal Fusobacterium nucleatum for the diagnosis of colorectal tumor: A systematic review and meta‐analysis

et al. 2019

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The fecal Fusobacterium nucleatum has been reported as a potential noninvasive biomarker for colorectal tumor in several studies, but its exact diagnostic accuracy was ambiguous due to the wide range of sensitivity and specificity. To assess the diagnostic accuracy of fecal F. nucleatum for colorectal tumor, we searched electronic databases including PubMed, Cochrane Library, Embase, and Web of Science, without any date and language restrictions. Two reviewers independently extracted data and appraised study quality with Quality Assessment of Diagnostic Accuracy Studies. We included ten studies comprising 13 cohorts for colorectal cancer (CRC) and seven cohorts for colorectal adenoma (CRA). A total of 1450 patients and 1421 controls for CRC and 656 patients and 827 controls for CRA were included. The pooled sensitivity and specificity of fecal F. nucleatum for CRC were 71% (95% CI, 61%‐79%) and 76% (95% CI, 66%‐84%), with the area under the receiver‐operating characteristics (AUC) curve of 0.80 (95% CI, 0.76‐0.83). The pooled sensitivity and specificity of fecal F. nucleatum for CRA were 36% (95% CI, 27%‐46%) and 73% (95% CI, 65%‐79%), with an AUC of 0.60 (95% CI, 0.56‐0.65). Substantial heterogeneity among studies existed, which was partly caused by DNA extraction kits, regions of study, sample size, and demographic characteristics of participants. Fecal F. nucleatum was valuable for the diagnosis of CRC although it performed below expectation. For CRA, the specificity of fecal F. nucleatum indicated the possibility of noninvasive screening. Subgroup analyses for adenoma were incomplete due to lack of data. Heterogeneity limited the credibility of the study.

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Section: Resultsmentioning

confidence: 95%

“…We calculated the pooled diagnostic accuracy of fecal F. nucleatum for Asian studies . For CRC, the pooled diagnostic accuracy of Asian studies was better than that of non‐Asian studies.…”

Section: Resultsmentioning

confidence: 99%

Fecal Fusobacterium nucleatum for the diagnosis of colorectal tumor: A systematic review and meta‐analysis

et al. 2019

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“…Several studies have utilized the abundance of multiple bacterial species to distinguish patients with CRC from healthy individuals. Among several bacterial candidates, F. nucleatum emerged as a key marker either when being quanti ed alone (16,21) or combined with other bacteria (13,17,43), speci cally Clostridium symbiosum (17). These ndings provide support for an accurate stool-based diagnostic test using markers targeting a limited number of microbial species.…”

Section: Discussionmentioning

confidence: 92%

WITHDRAWN: Fecal Enterotoxigenic Bacteroides fragilis-Peptostreptococcus stomatis-Parvimonas micra Biomarker for Noninvasive Diagnosis and Prognosis of Colorectal Laterally Spreading Tumor

Shen

et al. 2020

Preprint

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BackgroudUp to now, non-invasive prediction of laterally spreading tumor (LST) and adenoma recurrence after LST resection is inevitable. The purpose of this study was to identify a microbiome signature with a high predictive effect on LSTs and a microbiome with a high predictive effect on adenoma recurrence after LSTs colectomy.MethodsWe performed 16S rRNA sequencing in mucosal samples with 5 healthy controls (HC), 8 colorectal adenoma (CRA) patients and 11 LST patients. The differentiating microbiota in fecal samples was quantified by qPCR in 475 cases including 113 HC, 208 CRA patients, 109 LST patients and 45 colorectal cancer (CRC) patients. We applied linear discriminant analysis effect size analysis to identify taxa differentially abundant between cases and controls. ROC curve was used to evaluate the diagnostic value of bacterial candidates. Pairwise comparison of AUCs was performed using the Delong's test. Mantel-Haenszel hazard models were used to determine the effects of microbiota composition on recurrence free survival. ResultsLST microbial dysbiosis was characterized by relative high abundance of the genus Bacteroides-Streptococcus and the species enterotoxigenic Bacteroides fragilis (ETBF)-Peptostreptococcus stomatis (P. stomatis)-Parvimonas micra (P. micra). The abundance of ETBF, P. stomatis and P. micra were steadily increasing in LST and CRC groups. P.stomatis behaved stronger value on diagnosis of LST than the other two bacteria (AUC 0.887, 95%CI 0.842-0.931). The combination of P.stomatis, P.micra and ETBF (AUC 0.922, 95%CI 0.887-0.958) revealed strongest diagnostic power with 88.7% sensitivity and 81.4% specificity. ETBF, P. stomatis and P. micra were related to the malignant LST (PP. stomatis=0.0015, PP. micra =0.0255, PETBF =0.0169) and the abundance of IL-6. The relative high-abundance of P. stomatis were related to the adenoma recurrence after LST resection (HR = 3.88, P = 0.008). ConclusionsFecal microbiome signature (ETBF-P. stomatis-P. micra) can diagnose LSTs with high accuracy. ETBF, P. stomatis and P. micra were related to the malignant LST and P.stomatis exhibited a high predictive effect on the adenoma recurrence after endoscopic resection of LSTs. The signature bacteria of LST may provide a noninvasive alternative to early detect LST and predict the adenoma recurrence risk after resections.

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“…As the literature regarding these areas continues to expand, further characterization of their microbiomes will require genomic libraries including more taxa within the Actinobacteria or Fusobacteria phyla, which may not have appeared in earlier gut microbiome studies. This is becoming increasingly important as these taxa have been implicated in a number of health and disease states, such, as colon cancer (17–19).…”

Section: Resultsmentioning

confidence: 99%

Improving characterization of understudied human microbiomes using targeted phylogenetics

Rosa

Mihindukulasuriya

Hallsworth-Pepin

et al. 2019

Preprint

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29Whole genome bacterial sequences are required to better understand microbial functions, niche-30 specific bacterial metabolism, and disease states. Although genomic sequences are available for many 31 of the human-associated bacteria from commonly tested body habitats (e.g. stool), as few as 13% of 32 bacterial-derived reads from other sites such as the skin map to known bacterial genomes. To facilitate a 33 better characterization of metagenomic shotgun reads from under-represented body sites, we collected 34 over 10,000 bacterial isolates originating from 14 human body habitats, identified novel taxonomic 35 groups based on full length 16S rRNA sequences, clustered the sequences to ensure that no individual 36 taxonomic group was over-selected for sequencing, prioritized bacteria from under-represented body 37 sites (such as skin, respiratory and urinary tract), and sequenced and assembled genomes for 665 new 38 bacterial strains. Here we show that addition of these genomes improved read mapping rates of HMP 39 metagenomic samples by nearly 30% for the previously under-represented phylum Fusobacteria, and 40 27.5% of the novel genomes generated here had high representation in at least one of the tested HMP 41 samples, compared to 12.5% of the sequences in the public databases, indicating an enrichment of 42 useful novel genomic sequences resulting from the prioritization procedure. As our understanding of the 43 human microbiome continues to improve and to enter the realm of therapy developments, targeted 44 approaches such as this to improve genomic databases will increase in importance from both an 45 academic and clinical perspective. 46 47

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A Simple and Novel Fecal Biomarker for Colorectal Cancer: Ratio of Fusobacterium Nucleatum to Probiotics Populations, Based on Their Antagonistic Effect

Abstract: This study found that could play a role in microbiota dysbiosis via the secreted antagonistic substances against probiotics. Moreover, the ratio of to the important probiotics and was identified as a valuable biomarker for screening early CRC.

Cited by 127 publications

References 34 publications

Fecal Fusobacterium nucleatum for the diagnosis of colorectal tumor: A systematic review and meta‐analysis

Fecal Fusobacterium nucleatum for the diagnosis of colorectal tumor: A systematic review and meta‐analysis

WITHDRAWN: Fecal Enterotoxigenic Bacteroides fragilis-Peptostreptococcus stomatis-Parvimonas micra Biomarker for Noninvasive Diagnosis and Prognosis of Colorectal Laterally Spreading Tumor

Improving characterization of understudied human microbiomes using targeted phylogenetics

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