Fecal Microbiota Characteristics of Patients with Colorectal Adenoma Detected by Screening: A Population-based Study

• Fecal microbiota composition differed for patients with colorectal adenoma compared to normals.
• Most of the difference reflected 3-fold higher abundance of Proteobacteria in patients with adenoma.
• Population-wide microbiota screening is feasible and, if validated, could complement established early-detection programs.

BackgroundScreening for colorectal cancer (CRC) and precancerous colorectal adenoma (CRA) can detect curable disease. However, participation in colonoscopy and sensitivity of fecal heme for CRA are low.MethodsMicrobiota metrics were determined by Illumina sequencing of 16S rRNA genes amplified from DNA extracted from feces self-collected in RNAlater. Among fecal immunochemical test-positive (FIT +) participants, colonoscopically-defined normal versus CRA patients were compared by regression, permutation, and random forest plus leave-one-out methods.FindingsOf 95 FIT + participants, 61 had successful fecal microbiota profiling and colonoscopy, identifying 24 completely normal patients, 20 CRA patients, 2 CRC patients, and 15 with other conditions. Phylum-level fecal community composition differed significantly between CRA and normal patients (permutation P = 0.02). Rank phylum-level abundance distinguished CRA from normal patients (area under the curve = 0.767, permutation P = 0.006). CRA prevalence was 59% in phylum-level cluster B versus 20% in cluster A (exact P = 0.01). Most of the difference reflected 3-fold higher median relative abundance of Proteobacteria taxa (Wilcoxon signed-rank P = 0.03, positive predictive value = 67%). Antibiotic exposure and other potential confounders did not affect the associations.InterpretationIf confirmed in larger, more diverse populations, fecal microbiota analysis might be employed to improve screening for CRA and ultimately to reduce mortality from CRC.