During chemotherapy, 34% of breast cancer survivors (BCS) experience cancer treatment-related cognitive impairment (CRCI). CRCI degrades memory and executive function as well as quality of life. As the number of BCS is expected to increase by one million by 2030, there will also be an increase in the prevalence of CRCI. One understudied risk factor is diet, with an underlying mechanism being the gut microbiota. Post-treatment, increased fruit, vegetable, and fat consumption protects against CRCI in BCS. However, neither this relationship nor the underlying mechanisms, such as the gut microbiome, has been investigated during treatment, when CRCI begins. Adherence to a Mediterranean diet (Med Diet) has been shown to improve memory and to increase levels of Faecalibacterium prausnitzii, a gut bacterium associated with better cognitive scores in non-cancer populations. In BCS undergoing chemotherapy, this bacterium is linked with neurological toxicity. A Med Diet during treatment may therefore reduce CRCI incidence or severity via the gut microbiome. The objective of this study is to determine if diet is related to CRCI in BCS and if the gut microbiome is a mechanistic link. My central hypothesis is that higher adherence to components of a Med Diet, e.g., fruits, vegetables, monounsaturated fats, and fiber, will be related to higher scores on neuropsychological tests administered during chemotherapy, and that the gut microbiome will mediate this relationship. The aims of this study are as follows. Aim 1: Determine the relationship between components of a Med Diet, gut microbiome, and cognitive function in 30 BCS before, during, and after adjuvant chemotherapy treatment for breast cancer. Aim 2: Develop a Med Diet intervention for BCS by conducting semi-structured interviews among BCS who have recently completed treatment to understand their views and attitudes toward a Med Diet. Aim 3: Conduct a 12-week Med Diet pilot feeding study among 30 BCS undergoing adjuvant chemotherapy. To complete these aims, I need an interdisciplinary mentoring team to train me in 1) conducting research in cancer patients, 2) designing a controlled feeding trial, 3) qualitative data collection and analysis, and 4) advanced analysis of complex dietary, neuropsychological, and gut microbial datasets. Through training with this mentoring team and through the coursework and stellar facilities offered by my institution, I will complete the K99 phase of this proposal and thus (1) understand the relationship between diet, the gut microbiome, and cognition during breast cancer treatment, (2) understand BCS tastes and preferences of a Med Diet during treatment, (3) provide preliminary data for the submission of two R01 grant submissions; and (4) prepare me to lead a feeding trial during the R00 phase of the award to understand how the gut microbiome can be manipulated through a Med Diet to reduce CRCI. This K99/R00 will allow me to become an independent investigator leading gut microbiome-focused, patient-informed dietary trials to reduce CRCI’s negative impact.

This innovative study seeks to determine the role of dietary intake in supporting the growth of cognition- changing gut microbes and by-products that influence cognitive health in breast cancer survivors during receipt of chemotherapy. If proven correct, our study could provide compelling mechanistic evidence to explain how diet consumed during chemotherapy impacts the development or severity of cognitive impairment due to chemotherapy treatment in breast cancer survivors by modulating the gut microbiota and its products. The key outcomes include our first understanding of how diet and the gut microbiome impact the development or severity of cancer treatment-related cognitive impairment (CRCI), dietary or probiotic interventions designed to reduce incidence and severity of CRCI, and increased efforts to change local and nationwide policy to reimburse individuals with CRCI for the purchase of cognitively beneficial meals.