Integrating a Multi-Omics Cohort Study with a Medically Tailored Meal Intervention to Target Ultra-Processed Foods for Colorectal Cancer Prevention and Control - PROJECT SUMMARY/ABSTRACT Colorectal cancer (CRC) is a leading cause of cancer deaths in the US and is intricately tied to suboptimal diets. Ultra-processed foods (UPFs), which account for nearly 60% of Americans’ daily calories, emerge as an important risk factor for CRC. Proposed mechanisms include the production of pro-inflammatory metabolites, food processing-introduced carcinogens or additives (e.g., acrylamides, artificial sweeteners, or emulsifiers), and the obesogenic effect of UPFs. Growing evidence linked UPF-related metabolites and microbial species to CRC risk, supporting the hypothesis that UPFs promote CRC by inducing changes in the gut microbiome and metabolites. However, direct evidence evaluating this hypothesis remains scarce. Furthermore, there is a lack of evidence on the feasibility and efficacy of interventions addressing high UPF intake among at-risk populations and CRC patients, posing challenges in the development of cost-effective strategies for CRC prevention and control. The objective of this K99/R00 proposal is to identify gut microbial and metabolomic biomarkers of the UPF-CRC relationship and inform clinical interventions targeting UPFs to improve CRC survivorship. To achieve this objective, I will leverage multi-omics data from large prospective cohorts and integrate a medically tailored meal (MTM) intervention into the oncology care of CRC. The K99 research will focus on characterizing a gut microbial and a fecal metabolomic signature of UPFs and estimating their associations with CRC risk by utilizing comprehensive epidemiologic information and gut microbiome and fecal metabolome data from well-established cohorts – Nurses’ Health Study II (NHS II) and the Southern Community Cohort Study (SCCS) with 65% African American participants. The R00 research will evaluate the feasibility and initial efficacy of a single-arm 6-week MTM intervention targeting UPF intake in improving survivorship among 30 patients with stages I-III CRC recruited from hospitals in the Boston area. Individuals who are socioeconomically disadvantaged will be prioritized for enrollment. MTMs are of rapidly increasing interest to healthcare providers, patients, policymakers, funders, and the scientific community, owing to their promise to address specific health needs and diet-related disparities. Study findings will provide critical insights into the etiopathogenesis of UPF-CRC association relevant to diverse populations and inform the integration of medically tailored dietary interventions into oncology care to improve CRC survivorship. This proposal highly aligns with the NIH/NCI’s strategic plan for gut microbiome research and the use of food as medicine to improve cancer care. Under the mentorship of leading experts from Harvard T.H. Chan School of Public Health, Dana-Farber Cancer Institute, Massachusetts General Hospital, and Tufts Food is Medicine Institute, this rigorous training will expand my expertise in new areas, including gut microbiome and bioinformatics, clinical trial research, and MTM intervention strategy for oncology care, which are critical for my transition to being a productive independent investigator studying the diet-CRC relationship and translating epidemiologic evidence into innovative, affordable tactics for CRC prevention and control.
