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.