Gut Microbiota Signatures Associate with Chemotherapy-Related Adverse Events in Breast Cancer Patients

Background/Objectives: Chemotherapy-induced adverse events significantly impact cancer treatment outcomes and patient quality of life. Emerging evidence suggests that gut microbiota composition may influence individual susceptibility to chemotherapy toxicity. This study investigated associations between gut microbiome alterations and specific chemotherapy-related adverse events in breast cancer patients undergoing cancer treatment. Methods: We conducted a prospective cohort study of 81 breast cancer patients receiving chemotherapy between May 2018 and October 2022. Gut microbiome composition was analyzed using 16S rRNA sequencing across multiple taxonomic levels. Alpha diversity (Chao1 estimator) and beta diversity (PERMANOVA) analyses were performed to assess microbial richness and community structure. Linear discriminant analysis effect size (LEfSe) identified differentially abundant taxa, with Cohen's d effect sizes calculated with 95% confidence intervals and false discovery rate correction applied for multiple comparisons. Results: Significant microbiome-toxicity associations were identified across 42 taxa (FDR q < 0.05, effect sizes d = -1.60 to +1.67). Severe anemia demonstrated the strongest associations, with large effect size enrichment of Eubacteriaceae (d = 1.38), Anaerofilum (d = 1.42), and Eubacterium (d = 1.38). Severe neutropenia was characterized by depletion of butyrate-producing bacteria, particularly Eubacterium_hallii_group (d = -1.08). Thrombocytopenia showed dramatic depletion of Eubacterium limosum (53-fold reduction, d = -1.60). Hepatotoxicity (ALT elevation) was associated with depletion of Eubacterium_hallii_group (d = -0.99) and Burkholderia-Caballeronia-Paraburkholderia (d = -1.19). Hand-foot syndrome exhibited significantly elevated microbial diversity with depletion of Lachnospiraceae taxa. Most adverse events showed enrichment rather than depletion patterns, with 54.8% of significant associations demonstrating medium to large effect sizes. Conclusions: Specific gut microbiota signatures associated with distinct chemotherapy-related adverse events, suggesting potential microbiome-based biomarkers for toxicity prediction and personalized cancer treatment strategies.