Effect of programmed cell death protein-1 inhibitor combined with platinum-containing dual-agent chemotherapy regimen on gut microbiota in Lewis lung cancer model mice.

Purpose: To explore the effects of programmed cell death protein-1 (PD-1) combined with pemetrexed (PEM) and carboplatin (CARB) chemotherapy regimen on the gut microbiota in the Lewis lung cancer model mice compared to chemotherapy alone. Materials and methods: C57BL/6 J male mice aged 10-12 weeks were selected to establish the Lewis lung cancer model by planting tumors in the right forelimb, and were randomly divided into negative control group (NC group), chemotherapy group (PEM-CARB group), and chemotherapy combined with immunotherapy group (PEM-CARB-PD-1 group), with eight mice in each group. The total RNA of fecal bacteria was collected from the feces of mice in each group after two cycles of drug administration. 16S rRNA gene amplification and high-throughput sequencing were performed to analyze the Alpha diversity, Beta diversity, composition, and function in the gut microbiota. Results: The Alpha diversity was not statistically different between the PEM-CARB-PD-1 group and the PEM-CARB group (Shannon index: Conclusion: Combination therapy affects both "response-favorable taxa "and "response-unfavorable taxa associated with immunotherapy, and the ultimate impact remains dependent on the ratio of the two types of flora. Predicted metabolic pathway analysis using PICRUSt2 suggested that the combination regimen may not further reduce predicted functional pathway abundance beyond that observed with chemotherapy alone. However, these predictions require validation through direct metagenomic or metabolomic approaches.