From dysbiosis to systemic inflammation: The role of microplastics in inducing distal organ damage

Microplastics (MPs), a globally emerging contaminant, accumulate in the intestinal tract via ingestion and have become a significant source of local toxicity and systemic health risks. This review integrates the latest experimental and epidemiological evidence to systematically examine the cascade mechanism by which MPs transition from gut dysbiosis to systemic inflammation, and ultimately to Distal organ damage. It elucidates the core pathway through which MPs induce multi‑organ damage via the “gut microbiota–immunity–inflammation” axis. Within the intestine, MPs directly compromise the integrity of the physical barrier and, through oxidative stress, activate inflammatory signals. Specific surface properties, interfere with microbial ecology, thereby driving pronounced dysregulation of the composition and function of the gut microbiota. This state of dysregulation breaks down intestinal mucosal immune homeostasis, triggering the release of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) into the circulation and establishing ‘gut-derived systemic inflammation’. This inflammatory environment acts through a multi-organ communication network that spans the gut–liver (bile acid dysregulation, Kupffer cell activation), gut–kidney (inflammatory infiltration, oxidative damage), gut-brain (vagus nerve activation, neuroinflammation), and reproductive/developmental axes (penetration of the blood–testis/placental barrier, hormonal interference) to mediate Distal organ pathologies, including hepatic lipid dysregulation and fibrosis, kidney dysfunction, neurobehavioral alterations and reproductive/developmental toxicity. We focused on the pathogenic mechanisms of microplastics in vivo, summarized the current knowledge, and identified three priorities for future research: the specificity of MP–microbiota interactions, inter-organ crosstalk mechanisms, and microbiota-targeted intervention strategies. These studies provide a theoretical foundation for assessing the systemic health risks associated with microplastics.