Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity

SIMPLE SUMMARY: While lifesaving achievements have allowed cancer to be cured in many patients, survivors cured of cancer may suffer from long-term adverse treatment sequelae, substantially altering their quality of life and reintegration into normal life. Increasing evidence suggests the emerging role of the microbiome in chemotherapy-induced late effects affecting cognitive functions and the cardiovascular system. Moreover, existing data from animal models and patients with neurocognitive disorders and cardiovascular diseases outline the possibility that microbiota modulation might potentially prevent or mitigate the psycho-physiological deficits following chemotherapy and help to improve the behavioral comorbidities, cognitive functions, and quality of life in cancer survivors. ABSTRACT: Chemotherapy, targeting not only malignant but also healthy cells, causes many undesirable side effects in cancer patients. Due to this fact, long-term cancer survivors often suffer from late effects, including cognitive impairment and cardiovascular toxicity. Chemotherapy damages the intestinal mucosa and heavily disrupts the gut ecosystem, leading to gastrointestinal toxicity. Animal models and clinical studies have revealed the associations between intestinal dysbiosis and depression, anxiety, pain, impaired cognitive functions, and cardiovascular diseases. Recently, a possible link between chemotherapy-induced gut microbiota disruption and late effects in cancer survivors has been proposed. In this review, we summarize the current understanding of preclinical and clinical findings regarding the emerging role of the microbiome and the microbiota–gut–brain axis in chemotherapy-related late effects affecting the central nervous system (CNS) and heart functions. Importantly, we provide an overview of clinical trials evaluating the relationship between the gut microbiome and cancer survivorship. Moreover, the beneficial effects of probiotics in experimental models and non-cancer patients with neurocognitive disorders and cardiovascular diseases as well as several studies on microbiota modulations via probiotics or fecal microbiota transplantation in cancer patients are discussed.