Impacts of Vincristine and Prednisolone Chemotherapy on the Canine Gut Microbiota in Dogs Undergoing Treatment for Lymphoma

Abstract

Chemotherapy can have adverse gastrointestinal effects in dogs and people. The objective of this study was to assess the impact of vincristine and prednisolone/prednisone, as part of a CHOP chemotherapy [cyclophosphamide, hydroxydaunorubicin, oncovin (vincristine) and prednisolone/prednisone] protocol, on gastrointestinal dysbiosis in dogs with lymphoma. We hypothesised the first week of chemotherapy (administration of vincristine and prednisolone/prednisone, VCR/Pred) produces compositional and functional shifts in the canine faecal microbiota that are associated with increased dysbiosis. Faecal samples from canine lymphoma patients (n = 25) were compared for microbiota and metabolites before (pre-chemotherapy) and after the first week of VCR/Pred (post-chemotherapy). A dysbiosis index (DI) was calculated for each dog via quantitative PCR of seven bacterial taxa established for altered ratios in canine gastrointestinal dysbiosis: Faecalibacterium, Turicibacter, Escherichia coli, Streptococcus, Blautia, Fusobacterium and Peptacetobacter hiranonis (formerly Clostridium hiranonis). There was a significant increase in the DI post-chemotherapy compared to pre-chemotherapy (p = 0.021) concurrent with a significant decrease in faecal P. hiranonis concentrations post-chemotherapy (p = 0.0003). 16S rRNA amplicon sequencing analysis revealed a significant decrease in Enterococcaceae post-chemotherapy (p = 0.013). Targeted faecal lipid profiling identified markers of host and bacterial metabolic dysfunction that were altered following chemotherapy, including significant decreases in arachidonate (p = 0.0015), nervonate (p = 0.027), cholestanol (p = 0.011) and campesterol (p = 0.0035). These findings support that shifts in gut microbiota structure and function may contribute to gastroenteritis in dogs following the first week of VCR/Pred. Gut dysbiosis measures are important for improved treatment options that alleviate gastrointestinal complications associated with chemotherapy in animals and people.