Liver-spleen axis: Deciphering a crucial crosstalk in non-alcoholic fatty liver disease progression and therapeutic implications

Table 1 Microplastics and nanoplastics deeply permeate the liver and spleen, unsettling their natural functions

Domain	Organ/system	Mechanism	Cellular alterations	Physiological outcome
Immune dysfunction	Spleen	ROS-MAPK pathway activation; necroptosis; tissue atrophy	Reduced CD8+ T cells; increased CD4+/CD8+ ratio	Immunosuppression; impaired immune surveillance
Metabolic dysfunction	Liver	Disruption of transcriptomic networks governing nutrient handling and endocrine signaling	Altered lipid metabolism and insulin signaling pathways	Promotion of non-alcoholic fatty liver disease
Axis dysregulation	Liver-spleen axis	Impaired coordination of blood filtration and waste clearance	Accumulation of catabolic by-products; dysregulated inflammatory signaling	Increased susceptibility to metabolic and inflammatory disease
Systemic effects	Whole organism	Reprogramming of cellular survival and metabolic homeostasis	Persistent immune-metabolic imbalance	Progression to chronic organ disease

Microplastics (MPs) and nanoplastics (NPs) act as a dual-organ toxin that collapses the body’s metabolic and immune defenses. The synergy of their impact can be synthesized into three core failures: Immune failure (spleen): NPs trigger the reactive oxygen species (ROS)/mitogen-activated protein kinase pathway, leading to necroptosis and physical atrophy. This causes a critical “immune inversion” (reduced CD8⁺ T cells and increased CD4⁺/CD8⁺ ratio), resulting in systemic immunosuppression. Metabolic failure (liver): Chronic exposure serves as a catalyst for non-alcoholic fatty liver disease. MPs/NPs disrupt transcriptomic “machinery” responsible for nutrient absorption and endocrine signaling, rewiring the body’s fundamental metabolism. Systemic collapse (the axis): Because the liver and spleen work together to filter blood and manage waste, their simultaneous disruption creates a “pathological cascade.” The body loses its ability to clear catabolic waste while becoming hyper-susceptible to inflammatory and metabolic pathologies. Bottom line: MPs/NPs fundamentally reprogram cellular survival and metabolic homeostasis, transforming an environmental pollutant into a driver of chronic organ disease.