From Diet to Inflammasome: Ultra-Processed Foods as Upstream Drivers of NLRP3-Mediated Intestinal Inflammation in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic, immune-mediated gastrointestinal disorder. Although genetic susceptibility contributes to disease risk, it cannot explain the rapidly rising incidence, implicating environmental drivers. Diet has emerged as a key factor, especially the growing global consumption of ultra-processed foods (UPFs), characterised by extensive use of industrial food additives. While epidemiological studies increasingly associate UPF consumption with IBD risk, the underlying biological mechanisms remain insufficiently integrated. This review examines how UPF consumption contributes to IBD pathogenesis and whether dietary modification offers a more comprehensive therapeutic approach than immune inhibition alone. The evidence demonstrates that UPFs, particularly their additive components, disrupt gut homeostasis through converging mechanisms that closely align with IBD pathogenesis. By promoting dysbiosis, impairing mucus and epithelial barrier integrity, inducing endoplasmic reticulum stress, and activating inflammatory pathways such as the NLRP3 inflammasome, food additives sustain the self-perpetuating cycle of intestinal inflammation characteristic of IBD. Although immune dysregulation is central to disease expression, evidence indicates that it is largely driven by upstream disturbances in the gut environment. Current immune-targeted therapies control symptoms but do not address these upstream drivers. In contrast, dietary modulation, particularly reducing UPF exposure, offers a system-level strategy to restore gut homeostasis and complement existing treatments. Together, these findings support a shift in IBD research and management toward targeting upstream drivers of inflammation to improve long-term disease control and ultimately mitigate the growing global burden of IBD.