Effects Of Cisplatin And Doxorubicin Chemotherapy On Gut Microbiota In A Murine Osteosarcoma Model

Objective:Osteosarcoma is the most common malignant bone tumor among adolescents,and how to improve the survival rate of patients with osteosarcoma is a hot spot and difficult area of current research.The gut microbiota is closely associated with tumor progression and treatment in a variety of cancers.However,the alteration of the gut microbiota during the progression and chemotherapy of osteosarcoma remains poorly understood.This study aimed to explore the relationship between dysbiosis in the gut microbiota during osteosarcoma growth and chemotherapy treatment.Methods:We used BALB/c nude mice to establish osteosarcoma xenograft tumor models and administered cisplatin(CDDP)or doxorubicin(DOX)intraperitonially once every 2 days for a total of 5 times to establish effective chemotherapy models.Fecal samples were collected and processed for 16 S r RNA sequencing to analyze the composition of the gut microbiota.PICRUSt2(Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)was used to predict the functional differences in gut microbiota based on the differences in the composition of gut microbiota.We compared the differences in gut microbiota composition and function before and after osteosarcoma formation and before and after chemotherapeutic drug administration in mice.Results:We observed that the abundances of Colidextribacter,Lachnospiraceae＿NK4A136＿group,Lachnospiraceae＿UCG-010,Lachnospiraceae＿UCG-006,and Lachnoclostridium decreased,and the abundances of Alloprevotella and Enterorhabdus increased in the osteosarcoma mouse model group compared to those in the control group.In addition,genera,such as Lachnoclostridium and Faecalibacterium were more abundant in chemotherapy-treated mice than those in saline-treated mice.Furthermore,we observed that alterations in some genera,including Lachnoclostridium and Colidextribacter in the osteosarcoma animal model group returned to normal after CDDP or DOX treatment.Furthermore,the function of the gut microbiota was inferred through PICRUSt2,which indicated that metabolism-related microbiota was highly enriched and significantly different in each group.Conclusion:Lachnospiraceae and its metabolite butyrate may play an important role in the growth and treatment of osteosarcoma.This study helps to establish the link between gut microbiota and osteosarcoma growth and chemotherapy,providing a theoretical basis for further studies on the association of gut microbiota with the progression and treatment of osteosarcoma,and offering new ideas for potential therapeutic strategies for osteosarcoma.