Ultra-processed food ingredients as environmental contributors to chronic diseases and cancer: emerging evidence linking gut dysbiosis, inflammation, oxidative stress, and metabolic dysfunction

Ultra-processed foods (UPFs) are industrially manufactured formulations composed primarily of refined ingredients, modified fats, added sugars, salt, and numerous cosmetic additives designed to enhance palatability, appearance, texture, and shelf life. As UPFs constitute an increasingly large proportion of diets worldwide, growing epidemiological and experimental evidence links their consumption to a broad spectrum of chronic diseases, including obesity, metabolic syndrome, type 2 diabetes, cardiovascular disease, renal disorders, neurodegenerative conditions, and several forms of cancer. Common UPF constituents include refined flour, high levels of added sugars and artificial sweeteners, processed fats, sodium chloride, flavor enhancers, emulsifiers, thickeners, artificial colorants, preservatives, and processing-derived contaminants that may adversely affect human health. Emerging evidence suggests that the cumulative and interactive effects of these ingredients create a tumor-promoting biological milieu, herein referred to as onkoperigenesis (Greek: tumor-inducing environment). Multiple mechanisms appear to contribute to this process, including chronic low-grade inflammation, oxidative stress, genomic instability, epigenetic dysregulation, mitochondrial dysfunction, metabolic disturbances, and alterations in host immune responses. Many UPF additives and processing-related compounds increase the generation of reactive oxygen species, promote lipid peroxidation, induce DNA damage, and interfere with cellular repair mechanisms, thereby increasing susceptibility to malignant transformation and disease progression. A central pathway linking UPFs to chronic disease and cancer involves disruption of the gut microbiome. Emulsifiers, artificial sweeteners, preservatives, and other food additives have been shown to alter microbial diversity, reduce beneficial bacterial populations, impair gut barrier integrity, and promote intestinal permeability. These changes facilitate the systemic translocation of microbial products and inflammatory mediators, resulting in persistent immune activation. Diet-induced dysbiosis may further reduce the production of protective short-chain fatty acids, alter bile acid metabolism, and enhance signaling pathways associated with cellular proliferation, inflammation, and carcinogenesis. UPFs also contribute to metabolic dysfunction through effects on glucose regulation, insulin signaling, adiposity, and pancreatic β-cell function. These alterations promote insulin resistance, hyperinsulinemia, and chronic systemic inflammation, all of which are recognized contributors to both chronic disease development and tumor growth. In parallel, several food additives and processing-generated compounds have been associated with epigenetic modifications, endocrine disruption, apoptosis dysregulation, and mitochondrial impairment, creating conditions favorable for disease initiation and progression. This review examines the mechanistic pathways through which UPFs contribute to chronic diseases and cancer, emphasizing the interconnected roles of oxidative stress, inflammation, metabolic abnormalities, immune dysregulation, and microbiome disruption. Chronic conditions such as obesity, cardiovascular disease, renal dysfunction, neurological disorders, and skeletal abnormalities are discussed primarily as manifestations of these shared pathogenic mechanisms and as intermediary states that may further increase cancer risk. Collectively, current evidence indicates that UPFs promote a biological environment conducive to both chronic disease development and carcinogenesis. A deeper understanding of the individual and synergistic effects of UPF ingredients is essential for improving dietary risk assessment, informing regulatory policies, and developing effective public health strategies aimed at reducing the global burden of chronic diseases and cancer.