Abstract
Simple SummaryWhile 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.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.
Highlights
Modern oncology has produced substantial advancements in cancer treatment, prolonging the lives of patients
In a cohort of 155 germ-cell tumors (GCTs) survivors, we have shown that treatment with chemotherapy, radiotherapy, or both modalities was associated with self-reported impairment in several domains of cognitive functioning at a median of 10 years after treatment compared to controls treated with orchiectomy only [6]
The results showed that cognitive impairment and distinct psychological disorders are often linked to Chemotherapy-induced peripheral neuropathy (CIPN)
Summary
Modern oncology has produced substantial advancements in cancer treatment, prolonging the lives of patients. Cancer survivors face the long-term side effects of cancer treatment, with a number of late complications increasing the risk of cardiovascular diseases, second malignant neoplasms, the impairment of fertility, peripheral neuropathy, renal toxicity, and several other chemotherapy-related delayed toxicities [3,4]. Increasing evidence from animal models and clinical studies has highlighted the significant impact of the gut microbiome on the efficacy of cancer therapy, concerning mainly immunotherapeutic and chemotherapeutic treatment modalities [22,23,24,25,26,27]. Some recent data link the altered microbiome composition to the late effects of treatment in cancer survivors [30,31,32], and several clinical trials regarding this issue have been already completed or are still ongoing (Table 1)
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