Abstract
BackgroundThe gut microbiota is an important modulator of immune, metabolic, psychological and cognitive mechanisms. Chemotherapy adversely affects the gut microbiota, inducing acute dysbiosis, and alters physiological and psychological function. Cancer among young adults has risen 38% in recent decades. Understanding chemotherapy’s long-term effects on gut microbiota and psycho-physiological function is critical to improve survivors’ physical and mental health, but remains unexamined. Restoration of the gut microbiota via targeted therapies (e.g. probiotics) could potentially prevent or reverse the psycho-physiological deficits often found in young survivors following chemotherapy, ultimately leading to reduced symptom burden and improved health.MethodsThis longitudinal study investigates chemotherapy induced long-term gut dysbiosis, and associations between gut microbiota, and immune, metabolic, cognitive and psychological parameters using data collected at < 2 month (T1), 3–4 months (T2), and 5–6 months (T3) post-chemotherapy. Participants will be 18–39 year old blood or solid tumor cancer survivors (n = 50), and a healthy sibling, partner or friend as a control (n = 50). Gut microbiota composition will be measured from fecal samples using 16 s RNA sequencing. Psychological and cognitive patient reported outcome measures will include depression, anxiety, post-traumatic stress disorder symptoms, pain, fatigue, and social and cognitive function. Dual-energy X-ray Absorptiometry (DXA) will be used to measure fat and lean mass, and bone mineral concentration. Pro-inflammatory cytokines, C-reactive protein (CRP), lipopolysaccharide (LPS), serotonin, and brain derived neurotrophic factor (BDNF) will be measured in serum, and long-term cortisol will be assayed from hair. Regression and linear mixed model (LMM) analyses will examine associations across time points (T1 – T3), between groups, and covariates with gut microbiota, cognitive, psychological, and physiological parameters.ConclusionKnowing what bacterial species are depleted after chemotherapy, how long these effects last, and the physiological mechanisms that may drive psychological and cognitive issues among survivors will allow for targeted, integrative interventions to be developed, helping to prevent or reverse some of the late-effects of treatment that many young cancer survivors face. This protocol has been approved by the Health Research Ethics Board of Alberta Cancer Committee (ID: HREBA.CC-19-0018).
Highlights
The gut microbiota is an important modulator of immune, metabolic, psychological and cognitive mechanisms
Knowing what bacterial species are depleted after chemotherapy, how long these effects last, and the physiological mechanisms that may drive psychological and cognitive issues among survivors will allow for targeted, integrative interventions to be developed, helping to prevent or reverse some of the late-effects of treatment that many young cancer survivors face
This protocol has been approved by the Health Research Ethics Board of Alberta Cancer Committee (ID: HREBA.CC-19-0018)
Summary
The gut microbiota is an important modulator of immune, metabolic, psychological and cognitive mechanisms. Understanding chemotherapy’s long-term effects on gut microbiota and psycho-physiological function is critical to improve survivors’ physical and mental health, but remains unexamined. Dysbiosis-induced systemic inflammation can independently and bidirectionally activate or exacerbate stress circuits, most notably the hypothalamic-pituitaryadrenal (HPA)-axis, via the vagus nerve [2, 5].Cancer treatments, especially chemotherapy, can drive microbial dysbiosis in the gut [6], alter immune, metabolic and HPA-axis function [7], as well as cause psychological and cognitive perturbations both acutely and, potentially in the longer-term [8, 9]. Understanding chemotherapy’s long-term effects on the gut microbiota and subsequent relationships with immune, metabolic, psychological and cognitive outcomes is of critical importance in order to improve young adult cancer survivors’ physical and psychosocial health, but remains unexamined. Based on the following model (Fig. 1), we plan to investigate whether chemotherapy treatments are related to long-term gut microbiota dysbiosis, and subsequent associations with immune, metabolic, psychological and cognitive outcomes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
