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

Abstract 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.