Polystyrene microplastics induce kidney injury via gut barrier dysfunction and C5a/C5aR pathway activation

Microplastic is an emerging environmental pollutant with potential health risks. Recent studies have shown that microplastic could impair gut homeostasis in mammals. Although it has been widely demonstrated that gut dyshomeostasis could impact renal health through the gut-kidney axis, the effects of microplastic-induced gut dyshomeostasis on renal health and underlying mechanisms are still largely unknown. In the current work, we found that polystyrene microplastics (PS-MPs) treatment impaired the gut barrier, increased urinary complement-activated product C5a levels and renal C5aR expression, leading to chronic kidney disease-related symptoms in mice. Restoring the gut barrier using an antibiotic mixture effectively alleviated PS-MPs-induced kidney injury, indicating the involvement of the gut-kidney axis in PS-MPs-induced renal injury. Moreover, it also mitigated PS-MPs-induced alterations in urinary C5a levels and renal C5aR expression, suggesting that the renal C5a/C5aR pathway might be involved in PS-MPs' impacts on the gut-kidney axis. Further experiments using a C5aR inhibitor, PMX53, verified the vital role of renal C5a/C5aR pathway activation in the development of kidney injury induced by PS-MPs. Collectively, our results suggest that PS-MPs induce kidney injury in mice by impairing the gut barrier, increasing C5a levels, and ultimately activating the renal C5a/C5aR pathway, high-lighting the crucial role of the gut-kidney axis in PS-MPs-induced kidney injury.