Abstract
PURPOSE: While gut microbiome dysbiosis is known to play a role in colorectal cancer (CRC) initiation and progression, its role in CRC recurrence remains unclear. This study investigates whether the gut microbiome is associated with CRC recurrence. PATIENTS AND METHODS: In a prospective observational cohort, preoperative fecal samples from patients with stage I to III CRC undergoing surgical resection were analyzed using 16S rRNA gene sequencing. Alpha diversity and beta diversity were compared between patients with and without recurrence, and differential abundance analyses were conducted to identify bacterial genera associated with recurrence risk. RESULTS: Among 294 patients, 61 (21%) patients developed recurrence during a median follow-up of 56 months, with a median time to recurrence of 19 months. Alpha diversity did not differ between groups, but beta diversity analysis revealed significantly distinct microbial clustering in patients with recurrence, particularly those with locoregional recurrence. Differential abundance analysis identified five bacterial genera associated with locoregional recurrence (Acidaminococcus, Alloprevotella, Butyrivibrio, Ruminococcaceae CAG-352, and Lachnospiraceae UCG-003), one with distant recurrence (Megamonas), and two with overall recurrence (Anaeroplasma, Porphyromonas). Stratifying patients into high- and low-abundance subgroups revealed that those with a high relative abundance of Porphyromonas had an increased risk of overall recurrence (hazard ratio, 2.80 [95% CI, 1.54 to 5.10]). CONCLUSION: Patients with CRC who develop locoregional recurrence exhibit a distinct preoperative fecal microbial composition compared with those without recurrence. Our findings provide novel insights into the role of the intestinal microenvironment in recurrence and identify Porphyromonas as a potential fecal biomarker for overall recurrence risk.