Dataset Information

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

ABSTRACT:

Objective

Up to now, non-invasive diagnosis of laterally spreading tumor (LST) and prediction of adenoma recurrence after endoscopic resection of LSTs is inevitable. This study aimed to identify a microbial signature with clinical significance of diagnosing LSTs and predicting adenoma recurrence after LSTs colectomy.

Methods

We performed 16S rRNA sequencing in 24 mucosal samples, including 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 with 113 HC, 208 CRA patients, 109 LST patients, and 45 colorectal cancer (CRC) patients. We identified differentially abundant taxa among cases and controls using linear discriminant analysis effect size analysis. ROC curve was used to evaluate diagnostic values of the bacterial candidates. Pairwise comparison of AUCs was performed by using the Delong's test. The Mantel-Haenszel hazard models were performed to determine the effects of microbial compositions on recurrence free survival.

Results

The microbial dysbiosis of LST was characterized by relative high abundance of the genus Lactobacillus-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 diagnosing 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 associated with malignant LST (P_P.stomatis = 0.0015, P_P.micra = 0.0255, P_ETBF = 0.0169) and the abundance of IL-6. The high abundance of P. stomatis was related to the adenoma recurrence after LST resection (HR = 3.88, P = 0.008).

Conclusions

Fecal microbiome signature (ETBF-P. stomatis-P. micra) can diagnose LSTs with high accuracy. ETBF, P. stomatis, and P. micra were related to malignant LST and P. stomatis exhibited high predictive value on the adenoma recurrence after resection of LSTs. The fecal microbiome signature of LST may provide a noninvasive alternative to early detect LST and predict the adenoma recurrence risk after resections of LSTs.

SUBMITTER: Shen X

PROVIDER: S-EPMC8144651 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Enterotoxigenic Bacteroides fragilis (ETBF) strains, which produce a 20-kDa zinc metalloprotease toxin (BFT), have been associated with diarrheal disease in animals and young children. Studying a collection of ETBF and nontoxigenic B. fragilis (NTBF) strains, we found that bft and a second metalloprotease gene (mpII) are contained in an approximately 6-kb pathogenicity island (termed B. fragilis pathogenicity island or BfPAI) which is present exclusively in all 113 ETBF strains tested (pattern I). Of 191 NTBF strains, 100 (52%) lack both the BfPAI and at least a 12-kb region flanking BfPAI (pattern II), and 82 of 191 NTBF strains (43%) lack the BfPAI but contain the flanking region (pattern III). The nucleotide sequence flanking the left end of the BfPAI revealed a region with the same organization as the mobilization region of the 5-nitroimidazole resistance plasmid pIP417 and the clindamycin resistance plasmid pBFTM10, that is, two mobilization genes (bfmA and bfmB) organized in one operon and a putative origin of transfer (oriT) located in a small, compact region. The region flanking the right end of the BfPAI contains a gene (bfmC) whose predicted protein shares significant identity to the TraD mobilization proteins encoded by plasmids F and R100 from Escherichia coli. Nucleotide sequence analysis of one NTBF pattern III strain (strain I-1345) revealed that bfmB and bfmC are adjacent to each other and separated by a 16-bp GC-rich sequence. Comparison of this sequence with the appropriate sequence of ETBF strain 86-5443-2-2 showed that in this ETBF strain the 16-bp sequence is replaced by the BfPAI. This result defined the BfPAI as being 6,036 bp in length and its precise integration site as being between the bfmB and bfmC stop codons. The G+C content of the BfPAI (35%) and the flanking DNA (47 to 50%) differ greatly from that reported for the B. fragilis chromosome (42%), suggesting that the BfPAI and its flanking region are two distinct genetic elements originating from very different organisms. ETBF strains may have evolved by horizontal transfer of these two genetic elements into a pattern II NTBF strain.