Leveraging Fecal Microbial Markers to Improve the Diagnostic Accuracy of the Fecal Immunochemical Test for Advanced Colorectal Adenoma

INTRODUCTION: Fecal immunochemical tests (FITs) detect colorectal adenoma inefficiently. The gut microbiota participates in colorectal cancer development. We aimed to explore fecal microbial signatures for advanced adenomas and evaluate their diagnostic value and complementary capacity to FIT. METHODS: Using 16S rRNA sequencing, we studied gut microbiota in feces from 1,546 subjects in a screening setting, including 268 patients with advanced adenomas, 490 patients with nonadvanced adenomas, and 788 healthy subjects. Feature selections were performed using linear discriminant analysis effect size, multivariate association with linear models, and least absolute shrinkage and selection operator. The diagnostic performance of microbial signatures and their auxiliary role to FITs and the added value of the Asia-Pacific Colorectal Screening score were evaluated. We applied 0.632+ bootstrapping to adjust the potential overfitting. RESULTS: We identified 13 microbial signatures to show the joint diagnostic value for advanced adenoma, with genus Tyzzerella 4 demonstrating the highest adjusted area under the curve (AUC) of 0.545 (95% confidence interval [CI], 0.520-0.610). The 13-bacteria increased the adjusted AUC to 0.607 (95% CI, 0.548-0.660). Compared with individual FIT (adjusted AUC = 0.527; 95% CI, 0.519-0.571), 13-bacteria and FITs collectively reached an adjusted AUC of 0.641 (95% CI, 0.579-0.691). At cutoff values yielding specificities of 90% and 80%, the adjusted sensitivities were 28.4% (95% CI, 19.3-36.8) and 41.1% (95% CI, 29.9-49.4), respectively. The Asia-Pacific Colorectal Screening score further boosted the adjusted AUC to 0.706 (95% CI, 0.648-0.750). DISCUSSION: In this study using fecal samples from a screening setting, the identified microbial signatures could complement FITs for detecting advanced adenomas. Gut microbiota can act as a promising tool to optimize the current colorectal cancer screening modalities.