Gut microbiome in association with chemotherapy‐induced toxicities among patients with breast cancer

Abstract Background Little research has focused on the relationship between gut microbiome and chemotherapy‐induced toxicity. Methods This prospective study involves 301 patients with breast cancer who had prechemotherapy stool samples collected. Gut microbiome was sequenced by shotgun metagenomics; associations with chemotherapy‐induced toxicities during first‐line treatment by gut microbial diversity, composition, and metabolic pathways with severe (i.e., grade ≥3) hematological and gastrointestinal toxicities were evaluated via multivariable logistic regression. Results High prechemotherapy α‐diversity was associated with a significantly reduced risk of both severe hematological toxicity (odds ratio [OR] = 0.94; 95% CI, 0.89–0.99; p = .048) and neutropenia (OR = 0.94; 95% CI, 0.89–0.99; p = .016). A high abundance of phylum Synergistota , class Synergistia, and order Synergistales were significantly associated with a reduced risk of severe neutropenia; conversely, enrichment of phylum Firmicutes C, class Negativicutes, phylum Firmicutes I, and class Bacilli A , order Paenibacillales were significantly associated with an increased risk of severe neutropenia ( p range: 0.012–2.32 × 10 –3 ; false discovery rate <0.1). Significant positive associations were also observed between severe nausea/vomiting and high Chao1 indexes, β‐diversity ( p < .05), 20 species belonging to the family Lachnospiraceae , Oscillospiraceae , and Ruminococcaceae ( p value range: 6.14 × 10 –3 to 1.33 × 10 –5 ; false discovery rate <0.1), and three metabolic pathways involved in reductive tricarboxylic acid cycle I and cycle II, and an incomplete reductive tricarboxylic acid cycle ( p < .01). Conversely, a high abundance of species Odoribacter laneus and the pathway related to the L‐proline biosynthesis II were inversely associated with severe nausea/vomiting. Conclusions Our study suggests that gut microbiota may be a potential preventive target to reduce chemotherapy‐induced toxicity.