Sucrose and Fat Dietary Consumption Impact on the Murine Microbiome During Progression and Treatment of Cancer

Abstract

Objectives This study aims to investigate how dietary patterns, in concert with progression of cancer and both surgical and therapeutic interventions, impact the diversity and abundance of the murine microbiome. Methods 116 c57BI/6 female mice (7–8 weeks old) post-ovariectomy, were placed into diet groups A) low-sucrose/high-omega-3; B) low-sucrose/low-omega-3; C) high-sucrose/high-omega-3; or D) high-sucrose/high-omega-3. Mice were inoculated with breast cancer cells, subjected to lumpectomy, and treated with chemotherapy (9 mg/kg doxorubicin/90 mg/kg cyclophosphamide; and half received saline). Fecal samples were collected for gut microbiome analysis over the course of experiment and processed for 16S ribosomal genetic profiling using QIAmp® PowerFecal® DNA kit. A genomic library was generated, using previously validated primers for the V4 region. Cleaned FASTQ files were then used to infer ASVs (Amplicon Sequence Variants). Results There is a clear dietary effect which interacts with microbial abundance. Multiple ASVs have shown to be positively associated with high fat consumption, though inverse effects, as well as timepoint and treatment effects, have also been noted. Although Akkermansia muciniphila is usually seen as a minor gut resident, the species was abundant in all samples. Over the progression of cancer, a consistent decrease in the alpha diversity of the microbiome was observed. Notably, this effect was somewhat mitigated by the introduction of chemotherapeutic agents. Conclusions The findings of this study provide the foundation for future investigation of cancer patients specimens, with the overall goal of treatment improvement, discomfort mitigation, and better overall quality of life. Funding Sources This study was completed using The Ohio State University Ohio Agricultural Research and Development Center Hatch Funds.