Introduction

Fecal microbiome composition may modulate efficacy of cancer therapy and risk of side effects in humans. Some chemotherapy agents may lead to reduced gut microbial diversity in humans. The relationship between microbiota and chemotherapy efficacy and tolerability has not been investigated in dogs. We aimed to evaluate 1) changes in fecal microbial diversity during a cycle of CHOP and 2) whether these changes correlated with adverse events or treatment response.

Methods

Eighteen dogs with lymphoma were prospectively enrolled, and stool samples were collected weekly for 6 weeks during CHOP. Fecal microbiome was analyzed by 16S rRNA amplicon sequencing using an established protocol. Treatment-associated differences in richness, alpha and beta diversity were determined by comparison to data from healthy controls (n=27) using factorial ANOVA and PERMANOVA.

Results

Dogs with lymphoma had decreased fecal microbial diversity when compared with healthy controls at baseline (p=0.0002) and throughout treatment (p=0.0002, 0.0039, 0.0001). Alpha and beta diversity did not significantly change in dogs throughout a cycle of CHOP chemotherapy (p=0.284 and 0.93, respectively). Samples pre-treated with antibiotics were less diverse (alpha and beta diversity) than untreated samples (p=0.001, 0.0001). Some treated dogs developed an increased abundance of Proteobacteria during treatment.

Conclusion

The fecal microbiome of healthy dogs and dogs with lymphoma receiving CHOP is relatively stable over time, but dogs with lymphoma have reduced microbial diversity compared to healthy dogs. An increase in Proteobacteria abundance during treatment may be related to chemotherapy or antibiotic use.