Effect of chemotherapy on gut microbiota in patients with colorectal cancer

Introduction: The gut microbiota plays a crucial role in digestion, energy conversion, immune regulation, and disease resistance. Research has established a link between gut microbiota and the development and progression of colorectal cancer(CRC), noting variations in their composition within and around tumors, and gut microbiota may impact the effectiveness of drug therapies. Chemotherapy remains the cornerstone of CRC treatment, yet studies exploring its relationship with gut microbiota are still limited. Methods: In this study, 16S rRNA sequencing was performed to profile gut microbiota alterations in 20 patients with colorectal adenocarcinoma before and after chemotherapy, and to further explore the association between first-line chemotherapy and gut microbiota composition. All participants received the FOLFOX6 chemotherapy regimen, and fecal samples were collected pre- and post-treatment, aiming to elucidate the connection between chemotherapy and gut microbiota by analyzing alterations in microbial composition, diversity, and richness across different chemotherapy cycles. Results: Following the first chemotherapy cycle, Chao1 index indacate there is a decline in gut microbiota richness among CRC patients (P < 0.01), along with notable shifts in microbial composition. Specifically, the phyla Firmicutes and Bacteroides decreased, while Proteobacteria, Actinobacteria, and Verrucomicrobia increased in abundance. Comparative analyses of gut microbiota profiles across sequential chemotherapy cycles revealed no statistically significant intergroup differences in the Chao 1 and Simpson indices (all P > 0.05). As chemotherapy cycles proceeded, the gut microflora did not show regular dynamic changes with the progression of chemotherapy cycles. KEGG functional gene prediction analysis indicated that chemotherapy-induced alterations in gut microbiota composition were linked to common chemotherapy side effects, including metabolic, immune, hematological, and neurological disturbances. Discussion: Our results demonstrate that chemotherapy has a certain correlation with the composition of gut microbiota in patients with colorectal cancer, and these microbial changes show a potential association with chemotherapy-related adverse events.