Intestinal Dysbiosis and Development of Cardiometabolic Disorders in Childhood Cancer Survivors: A Critical Review

Abstract

Significance: Survivors of pediatric cancers have a high risk of developing side effects after the end of their treatments. Many potential factors have been associated with the onset of cardiometabolic disorders (CMD), including cancer disease itself, chemotherapy, hormonal treatment, radiotherapy, and genetics. However, the precise etiology and underlying mechanisms of these long-term complications are poorly understood. Recent Advances: Greater awareness is currently paid to the role of microbiota in the emergence of cancers and modulation of cancer therapies in both children and adults. Alterations in the composition and diversity of intestinal microbiota can clearly influence tumor development and progression as well as immune responses and clinical output. As dysbiosis is closely linked to the development of host metabolic diseases, including obesity, metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease, it may increase the risk of CMD in cancer populations. Critical Issues: Only limited studies targeting the profile of intestinal dysbiosis before and after cancer treatment have been conducted. Further, the exact contribution of intestinal dysbiosis to the development of CMD in cancer survivors is poorly appreciated. This review intends to clarify the influence of gut microbiota on CMD in childhood cancer survivors, elucidate the potential mechanisms, and evaluate the latest research on the interplay between diet/food supplement, microbiota, and cancer-related CMD. Future Directions: The implication of intestinal dysbiosis in late metabolic complications of childhood cancer survivors should be clarified. Intervention strategies could be developed to reduce the risk of survivors to CMD. Antioxid. Redox Signal. 34, 223-251.

Keywords: cancer survivors; dysbiosis; gut microbiota; inflammation; metabolic syndrome; oxidative stress.