Fecal microbial DNA markers serve for screening colorectal neoplasm in asymptomatic subjects

Background and Aim We have previously shown that fecal microbial markers might be useful for non-invasive diagnosis of colorectal cancer (CRC) and adenoma. Here, we assessed the application of microbial DNA markers, as compared with and in combination with fecal immunochemical test (FIT), in detecting CRC and adenoma in symptomatic patients and asymptomatic subjects. Methods We recruited 676 subjects [210 CRC, 115 advanced adenoma (AA), 86 non-advanced adenoma, and 265 non-neoplastic controls], including 241 symptomatic and 435 asymptomatic subjects. Fecal abundances ofFusobacterium nucleatum, aLachnoclostridium sp. m3,Bacteroides clarus, andClostridium hathewayiwere quantified by quantitative PCR. Combining score of the four microbial markers (4Bac) and diagnostic prediction were determined using our previously established scoring model and cutoff values and FIT with a cutoff of 100 ng Hb/mL. Results 4Bac detected similar percentages of CRC [85.3% (95%CI: 79.2-90.2%)vs84.9% (68.1-94.9%)] and AA [35.7% (12.8-64.9%)vs38.6% (29.1-48.8%)], while FIT detected more CRC [72.1% (63.7-79.4%)vs66.7% (48.2-82.0%)] and AA [28.6% (8.4-58.1%)vs16.8% (10.1-25.6%)], in symptomaticvsasymptomatic subjects, respectively. Focusing on the asymptomatic cohort, 4Bac was more sensitive for diagnosing CRC and AA than FIT (P < 0.001), with lower specificity [83.3% (77.6-88.0%)vs98.6% (96.0-99.7%)]. FIT failed to detect any non-advanced adenoma [0% (0.0-4.2%)] compared with 4Bac [41.9% (31.3-53.0%),P < 0.0001]. Combining 4Bac with FIT improved sensitivities for CRC [90.9% (75.7-98.1%)] and AA [48.5% (38.4-58.7%)] detection. Conclusion Quantitation of fecal microbial DNA markers may serve as a new test, stand alone, or in combination with FIT for screening colorectal neoplasm in asymptomatic subjects.

Automated summary

This study examined the application of microbial DNA markers in diagnosing colorectal cancer and adenoma compared to fecal immunochemical test (FIT). The results showed that microbial markers were more sensitive for detecting CRC and AA in asymptomatic subjects, but with lower specificity, while combining with FIT improved sensitivity for diagnosis.