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

Background: The occurrence and development of gastric cancer are closely related to the gut microbiota. Previous studies have found that the combination of anticancer bioactive peptides (ACBP) and oxaliplatin (OXA) has a significant therapeutic effect on gastric cancer. However the impact of ACBP-OXA on the gut microbiota was still unclear.

Methods: We established a nude mouse model of ACBP-OXA for gastric cancer and studied the diversity of gut microbiota and fecal metabolomics, and the correlation between gut microbiota and metabolites.

Results: ACBP-OXA has a significant regulatory effect on the gut microbiota. 16s rRNA research has found that in phylum, the relative abundance of Firmicutes and Bacteroidetes changed significantly after the ACBP-OXA group. Specifically, the relative abundance of Firmicutes decreased and Bacteroidetes increased. In the genus, while relative abundance of the Lachnospiraceae NK4AB6 group decreased in the ACBP-OXA group and the relative abundance of odpribacter and bacteroides increased. The relative abundance of Lactobacillus increased in the ACBP group, while the relative abundance of Staphylococcus decreased in the ACBP-OXA and OXA groups. GO and KEGG studies have found that the ACBP-OXA mechanism is related to metabolism and immunity. Through metabolomics research, this study found that differential metabolites were related to Neolignans, Lipids, and lipids that are involved in tyrosine metabolism, unsaturated fat acid biosynthesis, and Phenylalanine metabolism α- Biological processes. Combining metabolomics with 16s rRNA sequencing, it was found that amino acid-related metabolites are associated with bacterial genera such as Jetgalilicus, Staphylococcus, and Proteiniphilum.

Conclusion: The combination therapy of ACBP-OXA and ACBP-alone may improve and restore the gut microbiota of nude mice with gastric cancer by altering the distribution, diversity, and structure of the gut microbiota, which may be the key to inhibiting the occurrence and development of gastric cancer. This study provides a new direction for further research on the application of ACBP-OXA in the treatment of gastric cancer.