Processed Diets and Food Additives Shape the Gut Microbiota and Chronic Disease Risk Across the Life Course-A Three-Layer Ecosystem Disruption Model (TLED) Model.

Abstract

Ultra-processed foods (UPFs) represent a distinct dietary paradigm characterized by structurally simplified food matrices and chronic exposure to multiple additives, including emulsifiers, artificial sweeteners, and preservatives. Rather than acting in isolation, these compounds operate within a multi-additive environment that reshapes the gut ecosystem through convergent mechanisms. Emerging evidence suggests that additive-rich ultra-processed dietary environments may disrupt the gut ecosystem through three interconnected layers: (1) structural impairment of the intestinal barrier, including mucus erosion and tight-junction destabilization; (2) microbial metabolic shifts marked by short-chain fatty acid depletion, altered bile acid signaling, and enrichment of lipopolysaccharide-producing taxa; and (3) immune and inflammatory reprogramming promoting low-grade systemic inflammation. These processes collectively reduce ecosystem resilience-the capacity of the gut microbiota to resist and recover from perturbation. Vulnerability to additive-driven dysbiosis varies across the life course. During infancy, incomplete ecosystem stabilization may increase susceptibility to long-term ecological imprinting, whereas in older age, reduced microbial diversity and immune remodeling may impair recovery capacity following dietary stressors. In contrast, fiber-rich, minimally processed dietary patterns appear to enhance microbial resilience by reinforcing functional redundancy, metabolic buffering, and barrier integrity. Although much mechanistic evidence has been derived from experimental models, accumulating human data support the biological plausibility of additive-associated microbiota alterations. By integrating multi-additive exposure, ecosystem disruption, life-course modulation, and resilience within a unified framework, this review provides a mechanistically coherent model linking ultra-processed dietary environments to microbiota-mediated chronic disease risk. Here, we formalize this integrative perspective as the Three-Layer Ecosystem Disruption (TLED) Model.