Characterization of the gut microbiome in an osteosarcoma mouse model

Abstract

Compelling evidence has mounted surrounding the relationship between the gut microbiome and many intestinal and extraintestinal cancers. Few studies exist investigating the relationship between the gut microbiome and sarcoma. We hypothesize that the presence of distant osteosarcoma induces change to the profile of flora within the mouse. Twelve mice were used for this experiment: six were sedated and received an injection of human osteosarcoma cells into the flank, while six served as controls. Baseline stool and weight were collected. Tumor size and mouse weight were recorded weekly, and stool samples were collected and stored. Fecal microbiomes of the mice were profiled by 16S rRNA gene sequencing and analyzed for alpha diversity, relative abundances of microbial taxa, and abundance of specific bacteria at different time points. Alpha diversity was increased in the osteosarcoma group compared with the control group. The family Lachnospiraceae had the second strongest negative net average change in relative abundance over time in the osteosarcoma group whereas it had a positive net average change in the control group. An increased Firmicutes/Bacteroidota (F/B) ratio was observed in the osteosarcoma group relative to the control mice. These differences suggest that there may be an interplay between the gut microbiome and osteosarcoma. Clinical significance: Due to the paucity of literature available, our work can support novel research on this relationship and the development of new, personalized treatments for osteosarcoma.

Characterization of the gut microbiota and fecal metabolome in the osteosarcoma mouse model

“…Gut microbiota is involved in the development and progression of cancers [ 30 ]. Extra-intestinal tumor-associated microbiota has been identified in multiple human cancers, including breast, lung, and pancreatic cancers, melanoma tumors, and soft tissue sarcoma [ 31 , 32 ]. Alice Tzeng et al characterized the microbiome of human breast tissue.…”

“…Additionally, the tumor can be easily observed in athymic nude mice after subcutaneous injection due to the natural lack of hair [ 37 ]. In addition to analyzing tumor behavior, athymic mice have been used to examine the gut microbiome and its relation to cancer [ 32 ]. Therefore, this study established an athymic nude mouse model of OS to examine the abundance of gut microbiota and gut microbiota-derived metabolites and develop novel therapeutic strategies for OS.…”

The causal relationship between gut microbiota and bone mineral density: a Mendelian randomization study

“…By promoting the proliferation of intestinal and colonic cells, mediating the stability of the gut microbiota, and supporting mineral absorption in the intestines, supplementation with probiotics can enhance the mechanisms of healthy gut microbiota interactions, thereby increasing bone mineral density ( Seely et al, 2021 ). Furthermore, the development of osteosarcoma can alter the gut microbiome, indicating that there is also an interaction between osteosarcoma and the gut microbiota ( Le et al, 2023 ). The gut microbiota contributes to bone homeostasis through biochemical processes involving the immune, metabolism, and endocrine systems.…”