Chemotherapy-induced suppression of colorectal cancer-associated gut microbiota and modulation of host miRNA expression.

Abstract

Objectives: To characterize gut microbiome alterations in colorectal cancer (CRC) patients following cancer chemotherapy (CCT) and to explore associations with bacterial translocation and host miRNA dynamics.

Methods: Stool samples were prospectively collected from 20 CRC patients who had undergone radical surgery followed by adjuvant chemotherapy (CAPOX/mFOLFOX6). Stool samples were collected pre- and post-CCT. Microbial profiling was performed using 16S rRNA sequencing. Bacterial translocation was assessed by measuring serum anti-Lipopolysaccharides (LPS) IgA/IgG levels by ELISA. miRNA expression of miR-143 and miR-145 was quantified using qPCR.

Results: Post-CCT samples showed significant increases in gut microbiome diversity (P<0.05), with higher relative abundances of Porphyromonas, Peptostreptococcus, and Parvimonas, and decreased abundances of Faecalibacterium and Ruminococcaceae (P<0.005). Network analysis identified Peptostreptococcus and Parvimonas as possible CRC-associated taxa. Serum anti-LPS IgA and IgG levels significantly declined post-CCT, indicating reduced bacterial translocation. Concurrently, miR-143 and miR-145 levels increased more than twofold post-CCT (P<0.01), positively correlating with microbial shifts.

Conclusion: CCT induces significant remodeling of CRC-associated gut microbiota, characterized by suppression of pathogenic genera and enrichment of pro-inflammatory taxa. These changes align with reduced bacterial translocation and increased expression of tumor-suppressive miRNAs, suggesting that CCT exerts dual therapeutic effects by simultaneously modulating microbial communities and host molecular pathways.