Comprehensive 16s rRNA sequencing and metabolomics to investigate the effect of anticancer bioactive peptides combined with oxaliplatin on gastric cancer

背景: 胃癌的发生、发展与肠道菌群密切相关。既往研究发现抗癌生物活性肽(ACBP)与奥沙利铂(OXA)联合对胃癌有显着的治疗作用,但ACBP-OXA对肠道菌群的影响仍不清楚。 Methods: We established a nude mouse model of ACBP-OXA combined therapy for gastric cancer, the diversity of gut microbiota and fecal metabolomics were studied, and the correlation between gut microbiota and metabolites was analyzed. Results: ACBP-OXA联合疗法对肠道菌群具有很强的调节作用。16s rRNA研究发现,在门中,ACBP-OXA处理后,厚壁菌门和拟杆菌门的相对丰度发生显着变化,厚壁菌门的相对丰度下降,拟杆菌门的相对丰度增加。属内,ACBP-OXA组中毛螺菌科NK4AB6组的相对丰度降低,odpribacter和拟杆菌属的相对丰度增加。ACBP组乳酸菌相对丰度增加,ACBP-OXA和OXA组葡萄球菌相对丰度下降。GO和KEGG研究发现联合治疗机制与代谢和免疫有关。通过代谢组学研究,本研究发现差异代谢物与Benzenoids、Ligans、neoligans、其中脂质和脂类大多参与酪氨酸代谢、不饱和脂肪酸生物合成、苯丙氨酸代谢α-生物过程。将代谢组学与16s rRNA长寿素相结合,发现氨基酸相关代谢物与Jetgalilicus、Staphylococcus、Proteiniphilum等细菌属相关。 结论: ACBP与ACBP-OXA联合治疗可能通过改变肠道菌群的分布多样性和菌群结构来改善和恢复胃癌裸鼠的肠道菌群,这可能是抑制胃癌发生、发展的关键。该研究为进一步研究ACBP-OXA在胃癌治疗中的应用提供了新的方向。Background: The occurrence and progression of gastric cancer are closely associated with gut microbiota. Previous studies have demonstrated that the combination of anticancer bioactive peptide (ACBP) and oxaliplatin (OXA) exerts significant therapeutic effects on gastric cancer, but the impact of ACBP-OXA combined therapy on gut microbiota remains largely unclear. Methods: We established a nude mouse model of ACBP-OXA combined therapy for gastric cancer, investigated the diversity of gut microbiota and fecal metabolomics, and analyzed the correlation between gut microbiota and metabolites. Results: ACBP-OXA combined therapy exerts a strong regulatory effect on gut microbiota. 16S rRNA sequencing analysis revealed that at the phylum level, the relative abundances of Firmicutes and Bacteroidota changed significantly after ACBP-OXA treatment: the relative abundance of Firmicutes decreased, while that of Bacteroidota increased. At the genus level, the relative abundance of Lachnospiraceae NK4AB6 group decreased in the ACBP-OXA group, while the relative abundances of Odoribacter and Bacteroides increased. The relative abundance of Lactobacillus increased in the ACBP group, and the relative abundance of Staphylococcus decreased in both the ACBP-OXA and OXA groups. GO and KEGG enrichment analyses showed that the mechanism of combined therapy is related to metabolism and immunity. Metabolomic analysis revealed that differential metabolites include Benzenoids, Ligans, neoligans, among which lipids and lipid-like molecules mostly participate in biological processes such as tyrosine metabolism, unsaturated fatty acid biosynthesis, and phenylalanine metabolism. Combined metabolomic and 16S rRNA sequencing analyses showed that amino acid-related metabolites are correlated with bacterial genera such as Jetgalilicus, Staphylococcus, and Proteiniphilum. Conclusion: ACBP alone and ACBP-OXA combined therapy may improve and restore the gut microbiota of gastric cancer-bearing nude mice by altering the distribution diversity and community structure of gut microbiota, which may be the key to inhibiting the occurrence and progression of gastric cancer. This study provides a new direction for further research on the application of ACBP-OXA in gastric cancer therapy.