Gut microbiome structure prior to neoadjuvant chemoradiotherapy predicts risk of myelosuppression in rectal cancer patients

Abstract Background The gut microbiome plays a significant role in colorectal cancer development and treatment response. Neoadjuvant chemoradiotherapy (nCRT) is a cornerstone treatment for rectal cancer but is frequently associated with adverse effects, including myelosuppression. Previous studies suggest compositional and functional differences in the gut bacteria between patients who develop myelosuppression and those who do not. This study aimed to employ metagenomic sequencing to characterize the baseline gut microbiome composition and investigate its association with the subsequent risk of developing myelosuppression (NR means high-risk and R means low-risk for myelosuppression). Methods Baseline fecal samples were collected from rectal cancer patients prior to nCRT. Metagenomic sequencing was performed to comprehensively analyze the taxonomic composition, encompassing Bacteria, Archaea, Fungi, and Viruses, and metabolic functions of the gut microbial communities. Results Analysis of the gut microbiota revealed no significant differences in alpha diversitybetween the NR and R groups for myelosuppression. However, Principal Coordinates Analysis (PCoA) demonstrated a significant difference in beta diversity. The gut microbial composition was predominantly bacterial, followed by viruses, eukaryotes, and archaea. Conclusion This study indicates that while the overall richness and evenness of the baseline gut microbiome did not differ significantly between rectal cancer patients at NR and R for developing myelosuppression after nCRT, a striking contrast was observed in the overall structural composition (beta diversity) of the gut microbial communities between these risk groups. This finding suggests that specific structural features of the pre-treatment gut microbiome, rather than simple quantitative differences, may be associated with the risk of myelosuppression developing after chemoradiotherapy. (Acknowledgements: This study was supported by National Natural Science Foundation of China, Grant No. 32300085 to Zhenhui Chen, Grant No. 32370139 to Hongying Fan; Guangdong Basic and Applied Basic Research Foundation, Grant No. 2025A1515010567 to Zhenhui Chen)