Chemotherapy-induced gastrointestinal dysfunction: Mechanisms and integrative Western-Chinese medicine strategies

Chemotherapy-induced gastrointestinal dysfunction (CIGD) is a multifactorial clinical syndrome that substantially limits treatment tolerance, continuity, and quality of life in patients with cancer. Although targeted therapy and immunotherapy have expanded therapeutic options, chemotherapy remains a cornerstone of cancer treatment, and its gastrointestinal toxicities continue to pose major clinical challenges. Current evidence indicates that CIGD arises not from isolated lesions, but from interconnected pathological processes involving oxidative stress, mucosal barrier disruption, gut microbiota dysbiosis, immune amplification, and enteric nervous system (ENS) remodeling. In particular, microbiota-immune interactions and ENS-associated neuroimmune alterations may contribute to the persistence and amplification of tissue injury. Existing management strategies are still focused largely on symptom control and often do not adequately address the underlying biological drivers of dysfunction. In this review, we summarize the major mechanistic modules involved in CIGD and discuss a conceptual translational framework for mechanism-informed intervention. This framework includes: (1) targeted approaches aimed at interrupting key pathogenic loops, such as oxidative injury, microbial metabolite-related toxicity, and barrier dysfunction; (2) parameterizable integrative Western and Chinese medicine approaches, in which acupuncture and Chinese herbal formulae are considered as testable adjunctive modules alongside evidence-based supportive care; and (3) stratified management informed by interindividual variation in genetic background, drug metabolism, and microbiome features. On this basis, we further propose a working "niche medicine" framework that views CIGD as dysregulation of multicellular and molecular microenvironments across the gut ecosystem. This perspective may help connect mechanistic research with longitudinal monitoring, patient stratification, and multimodal intervention design, and may support a shift in CIGD management from predominantly symptomatic relief toward mechanism-guided restoration and recovery.