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Uncoupling Drug and Microbiota Contributions to Chemotherapy-Induced Gut Toxicity [RNA-seq]

ABSTRACT: Adverse effects of pharmaceutical agents are commonly attributed to direct drug toxicity. However, many drugs also disrupt gut microbial composition, and the resulting dysbiosis can influence drug metabolism, therapeutic efficacy, and host tissue responses. Disentangling microbiota-mediated effects from direct drug action remains a major challenge in understanding treatment-associated pathology. Here, we dissected the direct and microbiota-mediated effects of cytarabine (Ara-C), a widely used chemotherapeutic agent that frequently induces life-threatening gastrointestinal toxicity, on colonic barrier function and transcriptional responses. Using epithelial cell lines, ex vivo gut organ cultures, and in vivo models, we show that both Ara-C and its associated dysbiotic microbiota independently increase gut permeability, but through distinct molecular pathways: direct Ara-C exposure elicits interferon-driven inflammatory programs, whereas post-Ara-C microbiota activate mucosal defense and barrier-reinforcement gene sets. These findings establish chemotherapy-induced microbiota dysbiosis as an independent contributor to intestinal pathology and support microbiome-targeted strategies to mitigate gut toxicity.

ORGANISM(S): Mus musculus

PROVIDER: GSE303815 | GEO | 2025/11/12

REPOSITORIES: GEO

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Uncoupling Drug and Microbiota Contributions to Chemotherapy-Induced Gut Toxicity [16S rRNA-seq]

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