Intestinal inflammation mediates PFOA-induced sleep fragmentation and growth impairment in Drosophila

Perfluorooctanoic acid (PFOA), a persistent synthetic perfluorinated compound with widespread environmental distribution, bioaccumulates in organisms, raising concerns about potential adverse health effects. While previous studies suggest a correlation between PFOA exposure levels and altered sleep architecture, the specific consequences of chronic PFOA exposure on sleep regulation and the underlying mechanisms remain poorly understood. Utilizing Drosophila melanogaster as a model system, we investigated the effects of PFOA exposure. Our findings demonstrate that PFOA exposure resulted in significant growth inhibition, evidenced by reduced body size, and disrupted lipid metabolism. Furthermore, PFOA exposure significantly impacted sleep-wake patterns in a duration-dependent manner. Short-term exposure decreased nighttime sleep duration, whereas chronic exposure led to increased activity levels and severely fragmented sleep patterns. Mechanistically, we identified that chronic PFOA exposure significantly upregulated intestinal inflammation markers in Drosophila. Crucially, our results indicate that PFOA-induced intestinal inflammation is a key contributor to the observed sleep fragmentation. Notably, co-administration of the anti-inflammatory compound 1,8-Cineole mitigated both the intestinal inflammation and the sleep deficits caused by chronic PFOA exposure. This study elucidates a novel pathway linking chronic PFOA exposure, intestinal inflammation, and sleep disruption, providing valuable insights into the potential neurological consequences of persistent environmental pollutants.