Colorectal cancer therapy and nutrition: From ultra-processed consumption to metabolic reprogramming

Abstract

This narrative review examines the role of dietary patterns in colorectal cancer (CRC) development and management, with a focus on the diet-microbiome-metabolic reprogramming axis. CRC is one of the most prevalent and lethal malignancies worldwide, with pathogenesis shaped by genetic susceptibility, environmental exposures, and diet-related metabolic disturbances. High consumption of ultra-processed foods (UPFs), characterized by low fiber content and high levels of additives, has been associated with intestinal barrier dysfunction, dysbiosis, chronic inflammation, and oxidative stress, and a meta-analysis indicates that each 10% increase in UPF consumption corresponds to a 4% higher CRC risk. In contrast, metabolic dietary interventions, such as caloric restriction, fasting or fasting-mimicking diets, and ketogenic diets, have been primarily explored in preclinical models, demonstrating effects on tumor metabolism and inflammatory pathways. However, clinical evidence remains limited and heterogeneous, consisting mainly of small trials and observational studies with inconsistent protocols and variable adherence. This review critically synthesises current evidence by distinguishing between mechanistic insights and translational applicability. Well-designed clinical trials incorporating metabolic phenotyping and patient stratification are necessary to define the role of personalised nutrition as a potential adjunctive strategy in CRC prevention and treatment.

Keywords: Colorectal cancer; Nutrition; Ultra-processed foods; Gut; Gastrointestinal tract

Core Tip: Dietary modulation may represent a relevant preventive and supportive strategy in colorectal cancer. Dietary patterns characterized by higher intake of fiber and bioactive compounds, such as those derived from whole grains, fruits, and vegetables, and lower consumption of ultra-processed foods have been associated with improved intestinal and metabolic homeostasis. In selected patients and under professional supervision, metabolically targeted interventions such as time-restricted eating, caloric restriction, or fasting-mimicking diets may be considered as adjunctive approaches, based on their mechanistic links to tumor metabolism, inflammation, and host metabolic reprogramming. These strategies should be individualized, carefully monitored, and applied as complements to standard oncologic care.