Abstract
Background: Feline lymphoma is a common malignancy with variable response to chemotherapy. The gut microbiome plays a critical role in modulating immune function and drug metabolism, yet its influence on chemotherapy outcomes in cats remains poorly understood. Probiotics may offer a non-invasive strategy to enhance treatment efficacy and mitigate gastrointestinal side effects.Methods: A prospective, randomized, placebo-controlled trial was conducted in 32 client-owned cats with multicentric lymphoma receiving CHOP-based chemotherapy. Cats were randomly assigned to receive a multi-strain probiotic (n=16) or placebo (n=16) daily for 12 weeks. Fecal samples were collected at baseline, week 4, and week 12 for 16S rRNA gene sequencing. Chemotherapy response was assessed by RECIST criteria, and gastrointestinal toxicity was scored using a validated Veterinary Cooperative Oncology Group scale.Results: Probiotic supplementation significantly increased alpha diversity (Shannon index) at week 12 compared to placebo (p=0.02). The probiotic group exhibited enrichment of Lactobacillus and Bifidobacterium and a reduction in potentially pathogenic taxa. Overall response rate (complete + partial remission) was 81.3% in the probiotic group versus 56.3% in the placebo group (p=0.04). Grade 3-4 diarrhea occurred in 12.5% of probiotic-treated cats compared to 37.5% of controls (p=0.03).Conclusions: Probiotic administration during chemotherapy for feline lymphoma is associated with improved gut microbial diversity, higher remission rates, and reduced gastrointestinal toxicity. These findings support further investigation of microbiome modulation as an adjunctive strategy in veterinary oncology.